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MedWorm: Incretin Therapy



MedWorm.com provides a medical RSS filtering service. Over 7000 RSS medical sources are combined and output via different filters. This feed contains the latest news and research in the Incretin Therapy category.



Last Build Date: Tue, 29 Mar 2016 14:10:50 +0100

 



Incretin Hormone Receptors are Required for Normal Beta Cell Development and Function in Female Mice

Fri, 25 Mar 2016 23:00:00 +0100

In conclusion, a loss of the action of both incretin hormones results in direct impairment of beta cell function both in vivo and in vitro in a process that appears to be independent of the intestinally secreted incretin hormones. We therefore conclude that the incretin hormones together significantly impact both beta-cell function and beta-cell development. (Source: Peptides)

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No increased heart failure with incretin-based drugs

Thu, 24 Mar 2016 17:34:12 +0100

Incretin-based drugs, a type of medication used to treat type 2 diabetes, do not increase the risk of being hospitalized for heart failure relative to commonly used combinations of oral anti-diabetic drugs, according to a new study. (Source: ScienceDaily Headlines)



Incretin-Based Diabetes Drugs Not Tied to Heart Failure Hospitalizations (FREE)

Wed, 23 Mar 2016 23:00:00 +0100

By Kelly Young Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM Use of incretin-based drugs for type 2 diabetes — including dipeptidyl-peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 analogues — is not associated with increased risk for … (Source: Physician's First Watch current issue)



A Protein Preload Enhances the Glucose-Lowering Efficacy of Vildagliptin in Type 2 Diabetes

Wed, 23 Mar 2016 23:00:00 +0100

CONCLUSIONS In metformin-treated type 2 diabetes, a protein preload has the capacity to enhance the efficacy of vildagliptin to slow gastric emptying, increase plasma intact incretins, and reduce postprandial glycemia. (Source: Diabetes Care)



GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes

Wed, 23 Mar 2016 23:00:00 +0100

CONCLUSIONS PTDM is characterized by reduced glucose-induced insulin secretion and attenuated glucagon suppression during a hyperglycemic clamp. Similar to the case in type 2 diabetes, GLP-1 infusion seems to improve (insulin) or even normalize (glucagon) these pathophysiological defects. (Source: Diabetes Care)

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Cardiovascular Outcome Studies in Diabetes: How Do We Make Sense of These New Data?

Wed, 23 Mar 2016 23:00:00 +0100

Abstract Poorly controlled diabetes is characterized by premature cardiovascular mortality and morbidity. The mechanisms linking hyperglycemia with accelerated atherosclerotic disease have not been fully elucidated; however, are thought to be mediated through vascular inflammation, oxidative stress and endothelial dysfunction. The advent of incretin-based therapy, whether by increasing endogenous glucagon-like peptide (GLP)-1 and glucose-dependent inhibitory polypeptide by inhibition of their breakdown using di-peptidyl peptidase 4 inhibitors, or augmenting GLP-1 activity using either exendin-4-based drugs or synthetic GLP-1 analogs promised not just improvements in glycemic control, but improvements in endothelial function, lipid profiles and markers of vascular inflammation. As ...



Intestinal SGLT1 in Metabolic health and Disease.

Wed, 23 Mar 2016 23:00:00 +0100

Authors: Lehmann A, Hornby PJ Abstract The sodium/glucose cotransporter 1 (SGLT1/SLC5A1) is predominantly expressed in the small intestine. It transports glucose and galactose across the apical membrane in a process driven by a sodium gradient created by Na(+)/K(+)ATPase. SGLT2 is the major form found in the kidney and SGLT2 selective inhibitors are a new class of treatment for Type 2 Diabetes (T2DM). Recent data from patients treated with dual SGLT1/2 inhibitors or SGLT2-selective drugs such as canagliflozin (SGLT1 IC50= 663 nM) warrant evaluation of SGLT1 inhibition for T2DM. SGLT1 activity is highly dynamic, with modulation by multiple mechanisms in order to ensure maximal uptake of carbohydrates. Intestinal SGLT1 inhibition lowers and delays the glucose excursion following carb...



Incretin-based diabetes drugs don’t raise heart failure risk

Wed, 23 Mar 2016 21:00:00 +0100

Incretin-based antidiabetic drugs didn’t raise the risk of hospitalization for heart failure in an international observational study involving 1.5 million patients reported online March 24 in the New... (Source: Internal Medicine News)



Incretin-Based Therapy for Diabetes What a Cardiologist Needs to Know

Tue, 22 Mar 2016 05:43:04 +0100

Incretin-based therapies are effective glucose-lowering drugs that have an increasing role in the treatment of type 2 diabetes because of their efficacy, safety, and ease of use. Both glucagon-like peptide–1 receptor agonists and dipeptidyl peptidase–4 inhibitors are commonly used for glycemic control as adjuncts to metformin, other oral antiglycemic agents, or insulin. Glucagon-like peptide–1 receptor agonists may have additional effects, such as weight loss, that may be advantageous in obese patients. There is a large body of evidence from randomized controlled clinical trials supporting the cardiovascular safety of dipeptidyl peptidase–4 inhibitors and some glucagon-like peptide–1 receptor agonists, at least in the short term. However, concerns have been raised, particularly r...



GLP-1 and Hormonal Secretion in Posttransplant DiabetesGLP-1 and Hormonal Secretion in Posttransplant Diabetes

Thu, 17 Mar 2016 18:30:51 +0100

The incretin hormone glucagon-like peptide 1 (GLP-1) appears to correct the abnormal secretion of insulin and glucagon in posttransplantation diabetes (PTDM), researchers from Norway and Denmark report. Reuters Health Information (Source: Medscape Transplantation Headlines)



Evidence for neural contribution to islet effects of DPP-4 inhibition in mice.

Wed, 16 Mar 2016 23:00:00 +0100

Authors: Ahlkvist L, Omar B, Pacini G, Ahrén B Abstract It has been suggested that neural mechanisms may contribute to effects of the incretin hormones, and, therefore, also to the effects of dipeptidyl peptidase (DPP-4) inhibition. We therefore examined whether muscarinic mechanisms are involved in the stimulation of insulin secretion by DPP-4 inhibition. Fasted, anesthetized mice were given intraperitoneal saline or the muscarinic antagonist atropine (5mg/kg) before duodenal glucose (75mg/mouse), with or without the DPP-4 inhibitor NVPDPP728 (0.095mg/mouse), or before intravenous glucose (0.35g/kg) with or without co-administration with GLP-1 or glucose-dependent insulinotropic polypeptide (GIP) (both 3 nmol/kg). Furthermore, isolated islets were incubated (1h) in 2.8 and 11.1mM...



Postprandial Metabolism of Macronutrients and Cardiometabolic Risk: Recent Developments, Emerging Concepts, and Future Directions

Tue, 15 Mar 2016 00:00:00 +0100

Cardiovascular disease (CVD) is the leading cause of death in the United States. Although the role of habitual lifestyle factors such as physical activity and dietary patterns in increasing CVD risk has long been appreciated, less is known about how acute daily activities may cumulatively contribute to long-term disease risk. Here, the term acute refers to metabolic responses occurring in a short period of time after eating, and the goal of this article is to review recently identified stressors that can occur after meals and during the sleep-wake cycle to affect macronutrient metabolism. It is hypothesized that these events, when repeated on a regular basis, contribute to the observed long-term behavioral risks identified in population studies. In this regard, developments in research met...



The effect of 8 days of strict bed rest on the incretin effect in healthy volunteers

Tue, 15 Mar 2016 00:00:00 +0100

In conclusion, 8 days of bed rest induces insulin resistance, but we did not see evidence of an associated change in the incretin effect. (Source: Journal of Applied Physiology)

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The incretin effect in obese adolescents with and without type 2 diabetes: Impaired or intact?

Tue, 15 Mar 2016 00:00:00 +0100

Authors: Aulinger BA, Vahl TP, Prigeon RL, D'Alessio DA, Elder DA Abstract The incretin effect reflects the actions of enteral stimuli to promote prandial insulin secretion. Impairment of this measure has been proposed as an early marker of β-cell dysfunction, and described in type 2 diabetes (T2D), impaired glucose tolerance (IGT), and even obesity without IGT. We sought to determine the effects of obesity and diabetes on the incretin effect in young subjects with short exposures to metabolic abnormalities and few other confounding medical conditions. Subjects with T2D (n = 10; 18.0 ± 0.4 yr) or normal glucose tolerance (NGT), either obese (n = 11; 17.7 ± 0.4 yr) or lean (n = 8; 26.5 ± 2.3 yr), had oral glucose tolerance tests (OGTT) and isoglycemic infusions of glucose (IV-is...



No change in serum incretins levels but rise of leptin levels after smoking cessation: a pilot study.

Tue, 15 Mar 2016 00:00:00 +0100

In conclusions, smoking cessation increased leptin levels probably owing to weight gain while it did not influence incretin levels. PMID: 26988157 [PubMed - as supplied by publisher] (Source: Physiological Research)



Carbohydrate‐induced secretion of glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1

Mon, 14 Mar 2016 00:00:00 +0100

Abstract Glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) are the incretin hormones secreted from enteroendocrine K‐cells and L‐cells, respectively, by oral ingestion of various nutrients including glucose. K‐cells, L‐cells and pancreatic β‐cells are glucose‐responsive cells with similar glucose‐sensing machinery including glucokinase and an adenosine triphosphate‐sensitive K+ channel comprising KIR6.2 and sulfonylurea receptor 1. However, the physiological role of the adenosine triphosphate‐sensitive K+ channel in GIP secretion in K‐cells and GLP‐1 secretion in L‐cells is not elucidated. Recently, it was reported that GIP and GLP‐1‐producing cells are present also in pancreatic islets, and islet‐derived GIP and ...



Glucagon‐like peptide‐1 and cholecystokinin production and signaling in the pancreatic islet as an adaptive response to obesity

Mon, 14 Mar 2016 00:00:00 +0100

Abstract Precise control of blood glucose is dependent on adequate β‐cell mass and function. Thus, reductions in β‐cell mass and function lead to insufficient insulin production to meet demand, and result in diabetes. Recent evidence suggests that paracrine signaling in the islet might be important in obesity, and disruption of this signaling could play a role in the pathogenesis of diabetes. For example, we recently discovered a novel islet incretin axis where glucagon‐like peptide‐1 regulates β‐cell production of another classic gut hormone, cholecystokinin. This axis is stimulated by obesity, and plays a role in enhancing β‐cell survival. In the present review, we place our observations in the wider context of the literature on incretin regulation in the islet, and discu...



β‐Cell glutamate signaling: Its role in incretin‐induced insulin secretion

Mon, 14 Mar 2016 00:00:00 +0100

Abstract Insulin secretion from the pancreatic β‐cell (referred to as β‐cell hereafter) plays a central role in glucose homeostasis. Impaired insulin secretion is a major factor contributing to the development of diabetes and, therefore, is an important target for treatment of the disease. Cyclic adenosine monophosphate is a key second messenger in β‐cells that amplifies insulin secretion. Incretins released by the gut potentiate insulin secretion through cyclic adenosine monophosphate signaling in β‐cells, which is the basis for the incretin‐based diabetes therapies now being used worldwide. Despite its importance, the interaction between glucose metabolism and incretin/cyclic adenosine monophosphate signaling in β‐cells has long been unknown. A recent study showed that c...

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Glucagon‐like peptide‐1: The missing link in the metabolic clock?

Mon, 14 Mar 2016 00:00:00 +0100

Abstract Circadian expression of clock genes in peripheral tissues is critical to the coordinated regulation of intestinal digestive and absorptive functions, insulin secretion, and peripheral tissue nutrient deposition during periods of nutrient ingestion, thereby preventing metabolic dysregulation. As glucagon‐like peptide‐1 is a key incretin hormone that regulates glucose‐dependent insulin secretion, we hypothesized that this intestinal hormone is a player in the peripheral metabolic clock, linking nutrient ingestion to insulin secretion. We have now established that secretion of glucagon‐like peptide‐1 from the intestinal L cell shows a rhythmic pattern in rats and humans in vivo that is altered by circadian disruptors, such as constant light exposure, consumption of a West...



Mechanisms underlying glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 secretion

Mon, 14 Mar 2016 00:00:00 +0100

In conclusion, although K‐ and L cell populations overlap and share key molecular nutrient‐sensing mechanisms, subtle differences between the responsiveness of the different cell types might be exploited to differentially modulate glucose‐dependent insulinotropic peptide or glucagon‐like peptide‐1 secretion. This Minireview compares and to some degree contrast signalling mechanisms underlying glucose dependent insulinotropic polypeptide and glucagon‐like peptide‐1 secretion from K‐ and L‐cells. (Source: Journal of Diabetes Investigation)



Discovery of gastric inhibitory polypeptide and its subsequent fate: Personal reflections

Mon, 14 Mar 2016 00:00:00 +0100

Abstract The present review focuses initially on experimental studies that were designed to identify acid inhibitory factors, referred to as ‘enterogastrones,’ that ultimately led to the isolation of gastric inhibitory polypeptide (GIP), a 42‐amino acid polypeptide. GIP was shown to inhibit acid secretion in animal models, as well as stimulating gastric somatostatin secretion. However, its role in human gastric physiology is unclear. Further studies showed that GIP strongly stimulated the secretion of insulin, in the presence of elevated glucose, and this ‘incretin’ action is now considered to be its most important; an alternative for the GIP acronym, glucose‐dependent insulinotropic polypeptide, was therefore introduced. In the 1970s, GIP purified by conventional chromatograph...



Differential effects of oral and intravenous lipid administration on key molecules related to energy homeostasis.

Thu, 10 Mar 2016 00:00:00 +0100

CONCLUSIONS: Metabolic responses to lipids depend on the route of administration. Only IV lipids trigger a dose dependent FGF-21 secretion which is non-glucagon-mediated. IV lipids also induce hyperinsulinemia without concurrent decreases in glucose, a phenomenon observed in insulin resistant states. Orally administered lipids mostly affect gastrointestinal tract secreted molecules important in glucose and energy homeostasis such as glucagon, incretins-and PYY. PMID: 26964729 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Endocrinology and Metabolism)



GLP-1 based therapies: clinical implications for gastroenterologists

Wed, 09 Mar 2016 00:00:00 +0100

The gut-derived incretin hormone, glucagon-like peptide 1 (GLP-1) lowers postprandial blood glucose levels by stimulating insulin and inhibiting glucagon secretion. Two novel antihyperglycaemic drug classes augment these effects; GLP-1 receptor agonists and inhibitors of the GLP-1 degrading enzyme dipeptidyl peptidase 4. These so called GLP-1 based or incretin based drugs are increasingly used to treat type 2 diabetes, because of a low risk of hypoglycaemia and favourable effect on body weight, blood pressure and lipid profiles. Besides glucose control, GLP-1 functions as an enterogastrone, causing a wide range of GI responses. Studies have shown that endogenous GLP-1 and its derived therapies slow down digestion by affecting the stomach, intestines, exocrine pancreas, gallbladder and live...

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Glucagon-like peptide-1 regulates calcium homeostasis and electrophysiological activities of HL-1 cardiomyocytes

Sun, 06 Mar 2016 00:00:00 +0100

This study demonstrates GLP-1 may regulate HL-1 cell arrhythmogenesis through modulating calcium handling proteins. (Source: Peptides)



Artificial Sweeteners: A systematic review and primer for gastroenterologists.

Sat, 05 Mar 2016 21:43:02 +0100

Conclusions: Further research is needed to assess whether AS could be a potential cause of GI symptoms. This is especially pertinent in patients with irritable bowel syndrome, a population in whom dietary interventions are routinely utilized as a management strategy. PMID: 26932837 [PubMed - as supplied by publisher] (Source: Journal of Neurogastroenterology and Motility)



Diabetes: Concerns about long-term use of GLP-1 analogues

Fri, 04 Mar 2016 00:00:00 +0100

Nature Reviews Endocrinology 12, 186 (2016). doi:10.1038/nrendo.2016.33 Author: David Holmes Incretin mimetics (analogues of glucagon-like peptide 1 (GLP-1)) improve glycaemic control in patients with type 2 diabetes mellitus (T2DM) by stimulating pancreatic β cells to produce insulin. However, although clinical evidence supports short-term benefits of these agents, the consequences of long-term stimulation of healthy β (Source: Nature Reviews Endocrinology)



The incretin hormone glucagon-like peptide 1 increases mitral cell excitability by decreasing conductance of a voltage-dependent potassium channel.

Wed, 02 Mar 2016 00:00:00 +0100

This article is protected by copyright. All rights reserved. PMID: 26931093 [PubMed - as supplied by publisher] (Source: The Journal of Physiology)



Glucagon‐Like‐Peptide‐1 and Vitamin D: anti‐inflammatory response in diabetic kidney disease in db/db mice and in cultured endothelial cells

Tue, 01 Mar 2016 00:00:00 +0100

ConclusionsThe GLP‐1 analogue liraglutide prevented the inflammatory response observed in ECs exposed to a diabetic‐like environment and in db/db mice at the level of protein expression and significantly ameliorated the glomerular hypertrophy seen in the diabetic control group. This article is protected by copyright. All rights reserved. (Source: Diabetes/Metabolism Research and Reviews)

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Exenatide (a GLP-1 agonist) expresses anti-inflammatory properties in cultured human monocytes/macrophages in a protein kinase A and B/Akt manner.

Mon, 29 Feb 2016 12:18:02 +0100

CONCLUSIONS: We showed that exenatide skewed the macrophages phenotype toward anti-inflammatory phenotype and this effect is predominantly attributable to protein kinase A and to a less extent to B/Akt activation. PMID: 26922535 [PubMed - as supplied by publisher] (Source: Pharmacological Reports)



Glucagon-like Peptide-1 Regulates Calcium Homeostasis and Electrophysiological Activities of HL-1Cardiomyocytes

Mon, 29 Feb 2016 00:00:00 +0100

This study demonstrates GLP-1 may regulate HL-1 cell arrhythmogenesis through modulating calcium handling proteins. (Source: Peptides)



New Data Inform but Don't Confirm Incretin Diabetes Drugs SafetyNew Data Inform but Don't Confirm Incretin Diabetes Drugs Safety

Thu, 25 Feb 2016 09:10:34 +0100

Two new studies find that incretin-based drugs for the treatment of type 2 diabetes don't cause pancreatic cancer in the short term, but some may raise the risk of heart failure. Medscape Medical News (Source: Medscape Diabetes Headlines)



Effectiveness of Ipragliflozin, a Sodium-Glucose Co-transporter 2 Inhibitor, as a Second-line Treatment for Non-Alcoholic Fatty Liver Disease Patients with Type 2 Diabetes Mellitus Who Do Not Respond to Incretin-Based Therapies Including Glucagon-like Peptide-1 Analogs and Dipeptidyl Peptidase-4 Inhibitors

Thu, 25 Feb 2016 00:00:00 +0100

Conclusions Administration of SGLT-2 inhibitors led to not only good glycemic control, but also to a reduction in body weight, normalization of ALT levels, and a reduction in the FIB-4 index even in patients who did not respond to incretin-based therapy. (Source: Clinical Drug Investigation)



Mechanisms of Action of Liraglutide in Patients with Type 2 Diabetes Treated with High Dose Insulin.

Wed, 24 Feb 2016 00:00:00 +0100

CONCLUSIONS: Treatment with liraglutide significantly improved insulin secretion even in patients with long-standing T2D requiring high-dose insulin treatment. Liraglutide also decreased liver and subcutaneous fat, but did not alter glucagon secretion. PMID: 26909799 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Endocrinology and Metabolism)

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The Prospective Cardioprotective Effects of DPP-4 inhibition in the ischemic myocardium

Mon, 22 Feb 2016 00:00:00 +0100

Dipeptidyl peptidase (DPP)-4, also known as CD26, is an antigenic enzyme present on the surface of most cells and is related to immune response and apoptosis regulation [1]. As a non-specific enzyme, DPP-4 is associated with a large variety of substrates such as neuropeptides, growth factors and vasoactive peptides. DPP-4 also participates in the degradation of incretin hormones, thereby playing an important role in glucose metabolism [2]. DPP-4 inhibitors (DPP-4i) are a recent class of oral diabetic medication. (Source: Journal of Molecular and Cellular Cardiology)



Investigational insulin secretagogues for type 2 diabetes.

Fri, 19 Feb 2016 00:29:02 +0100

This article discusses: the new advances in the field of incretin-based therapies, glucokinase (GK) activators, free fatty acid receptor (FFAR) or G protein-coupled receptor (GPR) agonists (GPR40, GPR119, GPR120), imeglimin and some other insulin secretagogues with diverse mechanisms of action still in preclinical development. Expert opinion: New insulin secretagogues should offer major advantages over sulfonylureas and gliptins. The challenge is to avoid uncontrolled insulin secretion and minimize the risk of hypoglycemia, to protect cells from progressive loss of mass and function for a better durability of glucose control, and to offer a good safety profile. Numerous approaches are in development. However, it is too early to decide whether one new pharmacological class will emerge as a ...



A new angle for glp-1 receptor agonist: the medical economics argument Editorial on: Huetson P, Palmer JL, Levorsen A, et al. Cost-effectiveness of the once-daily glp-1 receptor agonist lixisenatide compared to bolus insulin both in combination with basal insulin for the treatment of patients with type 2 diabetes in Norway. J Med Econ 2015: 1-13 [Epub ahead of print].

Sat, 13 Feb 2016 13:53:03 +0100

Authors: Valencia WM, Florez HJ Abstract Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are relatively new medications for diabetes that offer a weight-loss profile that can be considered desirable for patients with both type 2 diabetes (T2D) and obesity. GLP-1 RA are effective in combination with insulin, and even slightly superior or at least equal to short-acting insulin in T2D; however, since they work in the incretin system, they may not be effective in long-standing disease. Additionally, only recently have publications reported their cardiovascular safety, and there is limited evidence for long-term effectiveness. The work presented by Huetson et al. offers a much needed perspective through a medical economic model for the long term cost-effectiveness of GLP-1 RA. The ...



The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions

Fri, 12 Feb 2016 00:00:00 +0100

Publication date: Available online 12 February 2016 Source:The Lancet Diabetes & Endocrinology Author(s): Michael A Nauck, Juris J Meier The incretin effect describes the phenomenon whereby oral glucose elicits higher insulin secretory responses than does intravenous glucose, despite inducing similar levels of glycaemia, in healthy individuals. This effect, which is uniformly defective in patients with type 2 diabetes, is mediated by the gut-derived incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The importance of the incretin effect for the maintenance of glucose homoeostasis is clearly established, and incretin-based therapies are among the most promising new therapies for type 2 diabetes. However, despite the effectiv...

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Delivery of Exenatide and Insulin Using Mucoadhesive Intestinal Devices.

Wed, 10 Feb 2016 00:00:00 +0100

This study validates the efficacy of mucoadhesive devices in promoting oral peptide delivery to improve patient compliance and dose adherence. PMID: 26864536 [PubMed - as supplied by publisher] (Source: Annals of Biomedical Engineering)



Liraglutide Compromises Pancreatic β Cell Function in a Humanized Mouse Model.

Wed, 10 Feb 2016 00:00:00 +0100

Authors: Abdulreda MH, Rodriguez-Diaz R, Caicedo A, Berggren PO Abstract Incretin mimetics are frequently used in the treatment of type 2 diabetes because they potentiate β cell response to glucose. Clinical evidence showing short-term benefits of such therapeutics (e.g., liraglutide) is abundant; however, there have been several recent reports of unexpected complications in association with incretin mimetic therapy. Importantly, clinical evidence on the potential effects of such agents on the β cell and islet function during long-term, multiyear use remains lacking. We now show that prolonged daily liraglutide treatment of >200 days in humanized mice, transplanted with human pancreatic islets in the anterior chamber of the eye, is associated with compromised release of human...



Reconfiguration of the small intestine and diabetes remitting effects of Roux-en-Y gastric bypass surgery

Fri, 05 Feb 2016 11:35:04 +0100

Purpose of review: Alterations in small intestinal physiology are proposed to play a causative role in the beneficial impact of Roux-en-Y gastric bypass on type 2 diabetes mellitus. The present article describes the key proposed mechanisms implicated with an emphasis on some of the newer findings in the field. Recent findings: Augmented incretin and diminished anti-incretin effects postsurgery are explored and a model proposed that reconciles the hindgut and foregut hypotheses of improved glycaemic control as being complementary rather than mutually exclusive. Synthesis of recent findings on postbypass changes in intestinal glucose handling then follows. Finally an updated view of the role of distal bile diversion and changes in the microbiota on enteroendocrine signalling is presented. ...



Meal sequence and glucose excursion, gastric emptying and incretin secretion in type 2 diabetes: a randomised, controlled crossover, exploratory trial

Fri, 05 Feb 2016 11:04:34 +0100

Conclusions/interpretation Meal sequence can play a role in postprandial glucose control through both delayed gastric emptying and enhanced incretin secretion. Our findings provide clues for medical nutrition therapy to better prevent and manage type 2 diabetes. Trial registration: UMIN Clinical Trials Registry UMIN000017434. Funding: Japan Society for Promotion of Science, Japan Association for Diabetes Education and Care, and Japan Vascular Disease Research Foundation. (Source: Diabetologia)



Interleukin-6 predicts inflammation-induced increase of Glucagon-like peptide-1 in humans in response to cardiac surgery with association to parameters of glucose metabolism

Wed, 03 Feb 2016 00:00:00 +0100

Conclusion: We found GLP-1 secretion to be increased in response to inflammatory stimuli in humans, which was associated to parameters of glucose metabolism and best predicted by IL6. (Source: Cardiovascular Diabetology)

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Stimulation of incretin secreting cells

Mon, 01 Feb 2016 00:00:00 +0100

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide-1 (GLP-1) are secreted from enteroendocrine cells in the gut and regulate physiological and homeostatic functions related to glucose control, metabolism and food intake. This review provides a systematic summary of the molecular mechanisms underlying secretion from incretin cells, and an understanding of how they sense and interact with lumen and vascular factors and the enteric nervous system through transporters and G-protein coupled receptors (GPCRs) present on their surface to ultimately culminate in hormone release. Some of the molecules described below such as sodium coupled glucose transporter 1 (SGLT1), G-protein coupled receptor (GPR) 119 and GPR40 are targets of novel therapeutics d...



Intestinal chemosensory mechanisms involving PYY and GLP-1

Mon, 01 Feb 2016 00:00:00 +0100

L cells are key players in the curative effect of bariatric surgery; one of the few current treatments for obesity. These cells, when stimulated by nutrients in the gut lumen or the blood stream, release PYY and the incretin GLP-1, both of which terminate feeding behaviour and control blood glucose levels. PYY exerts local anti-secretory mucosal effects and slows gut transit (Tough et al., 2011; Forbes et al., 2012). Using in vivo and in vitro techniques including polarised preparations of human and mouse intestinal mucosa we have elucidated several intestinal chemosensory mechanisms. (Source: Neuropeptides)



Novel Therapeutic Approaches in Diabetes.

Sat, 30 Jan 2016 12:16:02 +0100

Authors: Gallwitz B Abstract This chapter deals with novel therapeutic approaches, predominantly for type 2 diabetes. Incretin-based therapies utilize the effects of glucagon-like peptide-1 (GLP-1), which stimulates insulin and inhibits glucagon secretion in a glucose-dependent manner. Incretin-based therapies comprise injectable GLP-1 receptor agonists and orally active dipeptidyl peptidase-IV inhibitors. Both have a low hypoglycaemia risk. GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, dulaglutide, albiglutide) reduce glycated haemoglobin levels more effectively than oral antidiabetic agents do and lead to weight loss as well as a slight decrease in systolic blood pressure. The most common side effects are nausea and fullness, especially during the start of therap...



Bifidobacteria possess inhibitory activity against dipeptidyl peptidase‐IV

Thu, 28 Jan 2016 00:00:00 +0100

In this study, we investigated whether Bifidobacteria colonizing the human gut possess DPP‐IV inhibitory activity. Cell‐free intracellular extracts of 13 Bifidobacterium strains isolated from breast‐fed infant faecal samples were prepared and screened for DPP‐IV inhibitory activity, and two Bifidobacterium strains—Bif. longum BBMN68 and Bif. lactis Bb12—were used as reference strains. Most of the strains showed varying levels of DPP‐IV inhibitory property (7–27%). Strains of Bifidobacterium adolescentis IF1‐11 and Bifidobacterium bifidum IF3‐211 showed the greatest DPP‐IV inhibitory activity (27 and 25%) as well as good in vitro probiotic properties. This initial finding suggested that new beneficial function of Bifidobacteria is strain‐dependent and the strains ...



Atrial Natriuretic Peptide in the high normal range is associated with lower prevalence of insulin resistance.

Wed, 27 Jan 2016 00:00:00 +0100

CONCLUSION: Midlife exposure to ANP within the high normal range is associated with lower risk of insulin resistance. Further, midlife exposure to ANP within the high normal range is associated with greater post challenge GIP secretion at follow-up, possibly explaining the lower prevalence of insulin resistance. PMID: 26815880 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Endocrinology and Metabolism)

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Incretins, Pregnancy, and Gestational Diabetes.

Tue, 26 Jan 2016 00:00:00 +0100

Authors: Nikolica D, Al-Rasadib K, Al Busaidic N, Al-Wailib K, Banerjeed Y, Al-Hashmie K, Montalto G, Rizvi AA, Rizzo M Abstract The number of pregnant women affected by gestational diabetes mellitus (GDM) is increasing among Caucasians, and East Asians. GDM also increases the risk for later advent of type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease in both women and their offspring. The underlying mechanism of GDM is not fully elucidated. Incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), have been suggested to have a role in maternal metabolism and weight as well as fetal growth. These hormones might be implicated in mechanisms that compensate for the increment in glycemia and insulin resistance seen during pr...



Naturally-occurring TGR5 agonists modulating glucagon-like peptide-1 biosynthesis and secretion

Mon, 25 Jan 2016 00:00:00 +0100

This study examined the GLP-1 secretory activity of the ethnomedicinal plant, Fagonia cretica, which is postulated to possess anti-diabetic activity. After extraction and fractionation extracts and purified compounds were tested for GLP-1 and GIP secretory activity in STC-1 pGIP/neo cells. Intracellular levels of incretin hormones and their gene expression were also determined. Crude F. cretica extracts stimulated both GLP-1 and GIP secretion, increased cellular hormone content, and upregulated gene expression of proglucagon, GIP and prohormone convertase. However, ethyl acetate partitioning significantly enriched GLP-1 secretory activity and this fraction underwent bioactivity-guided fractionation. Three isolated compounds were potent and selective GLP-1 secretagogues: quinovic acid (QA) ...



Albiglutide: Is a better hope against diabetes mellitus?

Sun, 24 Jan 2016 16:12:02 +0100

Authors: Sharma AK, Thanikachalam PV, Rajput SK Abstract Type-2 diabetes mellitus (T2DM) is the chronic metabolic disorder which provokes several pitfall signalling. Though, a series of anti-diabetic drugs are available in the market but T2DM is still a huge burden on the developed and developing countries. Numerous studies and survey predict the associated baleful circumstances in near future due to incessant increase in this insidious disorder. The novelty of recent explored anti-diabetic drugs including glitazone, glitazaar and gliflozines seems to be vanished due to their associated toxic side effects. Brown and Dryburgh (1970) isolated an intestinal amino acid known as gastric inhibitory peptide (GIP) which had insulinotropic activity. Subsequently in 1985, another incretin gl...



Future glucose-lowering drugs for type 2 diabetes

Sat, 23 Jan 2016 00:00:00 +0100

Publication date: Available online 23 January 2016 Source:The Lancet Diabetes & Endocrinology Author(s): Clifford J Bailey, Abd A Tahrani, Anthony H Barnett The multivariable and progressive natural history of type 2 diabetes limits the effectiveness of available glucose-lowering drugs. Constraints imposed by comorbidities (notably cardiovascular disease and renal impairment) and the need to avoid hypoglycaemia, weight gain, and drug interactions further complicate the treatment process. These challenges have prompted the development of new formulations and delivery methods for existing drugs alongside research into novel pharmacological entities. Advances in incretin-based therapies include a miniature implantable osmotic pump to give continuous delivery of a glucagon-like pe...



Differences in β‐cell function and insulin secretion in Black vs. White obese adolescents: do incretin hormones play a role?

Fri, 22 Jan 2016 13:34:09 +0100

In conclusion, during an OGTT Black obese youth with NGT demonstrate a pronounced early insulin secretion jointly with heightened β‐cell glucose sensitivity, rate sensitivity, and potentiation factor. These racial disparities in β‐cell function and the pathophysiological components of T2D are unlikely to be attributed to incretin hormones and remain to be investigated further to explain the metabolic basis for the enhanced risk of T2D in back youth. (Source: Pediatric Diabetes)

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Treatment intensification in patients with inadequate glycemic control on basal insulin: rationale and clinical evidence for the use of lixisenatide and other glucagon‐like peptide‐1 receptor agonists

Wed, 20 Jan 2016 00:00:00 +0100

This article is protected by copyright. All rights reserved. (Source: Diabetes/Metabolism Research and Reviews)



Comparative Effects of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on Glucose Homeostasis and Incretin Hormones in Obese Type 2 Diabetic Patients: A One-Year Prospective Study

Wed, 20 Jan 2016 00:00:00 +0100

In conclusion, in morbidly obese T2DM patients, RYGB and VSG result in similar improvements of the glucose status in the face of different GI hormonal pattern. Weight loss is the key determinant of diabetes remission one year after surgery.[...]© Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text (Source: Hormone and Metabolic Research)



Role of Vasopressin in the Regulation of Renal Sodium Excretion: Interaction with Glucagon‐Like Peptide‐1

Wed, 20 Jan 2016 00:00:00 +0100

This article is protected by copyright. All rights reserved. (Source: Journal of Neuroendocrinology)



Mercaptoacetate blocks fatty acid-induced GLP-1 secretion in male rats by directly antagonizing GPR40 fatty acid receptors.

Wed, 20 Jan 2016 00:00:00 +0100

Authors: Li AJ, Wang Q, Dinh TT, Simasko SM, Ritter S Abstract Mercaptoacetate (MA) is an orexigenic agent reported to block fatty acid (FA) oxidation. Recently, however, we reported evidence from isolated nodose ganglion neurons that MA antagonizes the G-protein coupled long and medium chain FA receptor, GPR40. GPR40 mediates FA-induced secretion of the satietogenic incretin peptide, glucagon-like peptide 1 (GLP-1), by enteroendocrine L cells, as well as FA-induced enhancement of glucose stimulated insulin secretion. Our results in cultured nodose neurons suggest that MA would also block GPR40 in enteroendocrine cells controlling GLP-1 secretion. If so, this would suggest an alternative mechanism by which MA increases food intake. We tested the hypothesis that MA blocks FA-induced...



The effect of pregnane X receptor agonists on postprandial incretin hormone secretion in rats and humans.

Sun, 17 Jan 2016 01:36:02 +0100

In conclusion, PXR agonists do not affect the secretion of incretin hormones. The regulation of glucagon secretion by PXR may be sexually dimorphic in humans. The mechanism of disrupted glucose metabolism induced by PXR activation requires further study. PMID: 26769831 [PubMed - in process] (Source: Journal of Physiology and Pharmacology)

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The physiological role of glucagon-like peptide-1 in the regulation of renal function

Fri, 15 Jan 2016 00:00:00 +0100

This study aimed to test the hypothesis that blockade of GLP-1 receptor (GLP-1R) signaling at baseline influences renal salt and water handling. To this end, the GLP-1R antagonist exendin-9 (100 μg·kg–1·min–1) or vehicle was administered intravenously to overnight-fasted male Wistar rats for 30 min. This treatment reduced urinary cAMP excretion and renal cortical PKA activity, demonstrating blockade of renal GLP-1R signaling. Exendin-9-infused-rats exhibited reduced glomerular filtration rate, lithium clearance, urinary volume flow, and sodium excretion compared with vehicle-infused controls. Exendin-9 infusion also reduced renal cortical Na+/H+ exchanger isotope 3 (NHE3) phosphorylation at serine 552 (NHE3pS552), a PKA consensus site that correlates with reduc...



Significant Elevation of Serum Dipeptidyl Peptidase-4 Activity in Young-adult Type 1 Diabetes

Thu, 14 Jan 2016 00:00:00 +0100

Dipeptidyl peptidase 4 (DPP-4), also known as CD26, is a multifunctional transmembrane glycoprotein and widely recognized as a critical player in glucose homeostasis [1]. DPP-4 is a serine protease enzyme that inactivates incretin hormones, glucagon-like peptide (GLP)-1, and glucose-dependent insulinotropic peptide (GIP). GLP-1 and GIP are secreted from intestine after ingestion of meals and exert pivotal functions on metabolic homeostasis through enhancement of glucose-dependent insulin secretion from pancreatic β-cells, suppression of excessive glucagon secretion from α-cells, and other various bioactivities. (Source: Diabetes Research and Clinical Practice)



Cardiovascular Effects of Incretin-Based Therapies.

Thu, 14 Jan 2016 00:00:00 +0100

This article reviews the most recent CV outcome trials of the DPP-4 inhibitors (SAVOR-TIMI 53, EXAMINE, and TECOS) as evidence that the incretin-based therapies have acceptable CV safety profiles for patients with T2DM. The studies differ with regard to patient population, trial duration, and heart failure outcomes but show similar findings for CV death, nonfatal myocardial infarction, and stroke, as well as hospitalization for unstable angina. PMID: 26768240 [PubMed - in process] (Source: Annual Review of Medicine)



Glucagon-like peptide-1 and gastric inhibitory polypeptide: new advances

Wed, 13 Jan 2016 22:45:34 +0100

Purpose of review: Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) are gastrointestinal peptides that play an important role as incretin hormones in the regulation of plasma glucose and insulin secretion. GLP-1-based therapies have therefore been implemented as treatment for type 2 diabetes (T2D). The purpose of this review is to summarize novel treatment options for T2D with GLP-1-based therapies. In addition, both peptides have relevant extrapancreatic effects that have been further characterized recently and are summarized in this review. Recent findings: Novel findings regarding changes in GLP-1 secretion after bariatric surgery are highlighted, wherein GLP-1 plays a role in promoting body weight loss and diabetes remission. For T2D therapy, novel options with...



Trends in incidence, prevalence and prescribing in type 2 diabetes mellitus between 2000 and 2013 in primary care: a retrospective cohort study

Wed, 13 Jan 2016 00:00:00 +0100

Conclusions Prevalent cases of T2DM more than doubled between 2000 and 2013, while the number of incident cases increased more steadily. Changes in prescribing patterns observed may reflect the impact of national policies and prescribing guidelines on UK primary care. (Source: BMJ Open)

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Effect of meal composition on postprandial glucagon-like peptide-1, insulin, glucagon, C-peptide, and glucose responses in overweight/obese subjects

Tue, 12 Jan 2016 00:00:00 +0100

Conclusions GLP-1 and insulin responses were higher during the HP condition. However, no difference was found in blood glucose between conditions, and insulin sensitivity was higher during the HMF condition, indicating that a HMF meal may be optimal at regulating blood glucose in overweight/obese individuals without type 2 diabetes. (Source: European Journal of Nutrition)



Albiglutide: Is a better hope against diabetes mellitus?

Mon, 11 Jan 2016 00:00:00 +0100

Publication date: February 2016 Source:Biomedicine & Pharmacotherapy, Volume 77 Author(s): Arun K. Sharma, Punniyakoti V. Thanikachalam, Satyendra K. Rajput Type-2 diabetes mellitus (T2DM) is the chronic metabolic disorder which provokes several pitfall signalling. Though, a series of anti-diabetic drugs are available in the market but T2DM is still a huge burden on the developed and developing countries. Numerous studies and survey predict the associated baleful circumstances in near future due to incessant increase in this insidious disorder. The novelty of recent explored anti-diabetic drugs including glitazone, glitazaar and gliflozines seems to be vanished due to their associated toxic side effects. Brown and Dryburgh (1970) isolated an intestinal amino acid known as gast...



CEACAM2 in GLP-1 Secretion [Metabolism]

Fri, 08 Jan 2016 00:00:00 +0100

This study investigated whether CEACAM2 also regulates insulin secretion. Ceacam2 deletion caused an increase in β-cell secretory function, as assessed by hyperglycemic clamp analysis, without affecting insulin response. Although CEACAM2 is expressed in pancreatic islets predominantly in non-β-cells, basal plasma levels of insulin, glucagon and somatostatin, islet areas, and glucose-induced insulin secretion in pooled Cc2−/− islets were all normal. Consistent with immunofluorescence analysis showing CEACAM2 expression in distal intestinal villi, Cc2−/− mice exhibited a higher release of oral glucose-mediated GLP-1, an incretin that potentiates insulin secretion in response to glucose. Compared with wild type, Cc2−/− mice also showed a higher insulin excursion during the oral ...



Altered Expression of Uncoupling Protein 2 in GLP-1-producing Cells after Chronic High Glucose Exposure: Implications for the Pathogenesis of Diabetes Mellitus.

Wed, 06 Jan 2016 00:00:00 +0100

Authors: Urbano F, Filippello A, Di Pino A, Barbagallo D, Di Mauro S, Pappalardo A, Rabuazzo AM, Purrello M, Purrello F, Piro S Abstract Glucagon-like peptide-1 (GLP-1) is a gut L-cell hormone that enhances glucose-stimulated insulin secretion. Several approaches that prevent GLP-1 degradation or activate the GLP-1 receptor are being used to treat type 2 diabetes mellitus (T2DM) patients. In T2DM, GLP-1 secretion has been suggested to be impaired, and this defect appears to be a consequence rather than a cause of impaired glucose homeostasis. However, although defective GLP-1 secretion has been correlated with insulin resistance, little is known about the direct effects of chronic high glucose concentrations, which are typical in diabetes patients, on GLP-1-secreting cell function....



Diabetic and nondiabetic patients with nonalcoholic fatty liver disease have an impaired incretin effect and fasting hyperglucagonaemia

Tue, 05 Jan 2016 00:00:00 +0100

ConclusionsPatients with NAFLD have a reduced incretin effect and fasting hyperglucagonaemia, with the latter occurring independently of glucose (in)tolerance. (Source: Journal of Internal Medicine)

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Strategies to Make Ramadan Fasting Safer in Type 2 Diabetics: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials and Observational Studies

Fri, 01 Jan 2016 06:00:00 +0100

Abstract: Ramadan is the holy month for Muslims whereby they fast from predawn to after sunset and is observed by all healthy Muslim adults as well as a large population of type 2 diabetic Muslims. To determine the comparative effectiveness of various strategies that have been used for type 2 diabetic Muslim who fast during Ramadan. A systematic review and network meta-analysis of randomized controlled studies (RCT) as well as observational studies for patients with type 2 diabetes who fasted during Ramadan was conducted. Eight databases were searched from January 1980 through October 2015 for relevant studies. Two reviewers independently screened and assessed study for eligibility, assessed the risk of bias, and extracted relevant data. A network meta-analysis for each outcome was fitte...



Special Section

Fri, 01 Jan 2016 00:00:00 +0100

GLP-1 Pathway drugs (Incretin Therapy) for Diabetes Melitus: Physiology, Clinical Rationale and Implications for the Exocrine Pancreas. (Source: Pancreatology)



Dipeptidyl Peptidase 4 Inhibition Alleviates Shortage of Circulating Glucagon-Like Peptide-1 in Heart Failure and Mitigates Myocardial Remodeling and Apoptosis via the Exchange Protein Directly Activated by Cyclic AMP 1/Ras-Related Protein 1 Axis [Original Articles]

Thu, 31 Dec 2015 00:00:00 +0100

Conclusions— DPP4i restores cardiac remodeling and apoptosis caused by the pathological decline in circulating GLP-1 in response to pressure overload. EPAC1 is essential for cardiomyocyte survival via the cAMP/Rap1 activation independently of PKA. (Source: Circulation: Heart Failure)



Exciting Times for Pancreatic Islets: Glutamate Signaling in Endocrine Cells

Tue, 29 Dec 2015 00:00:00 +0100

Publication date: Available online 28 December 2015 Source:Trends in Endocrinology & Metabolism Author(s): Silke Otter, Eckhard Lammert Glutamate represents a key excitatory neurotransmitter in the central nervous system, and also modulates the function and viability of endocrine cells in pancreatic islets. In insulin-secreting beta cells, glutamate acts as an intracellular messenger, and its transport into secretory granules promotes glucose- and incretin-stimulated insulin secretion. Mitochondrial degradation of glutamate also contributes to insulin release when glutamate dehydrogenase is allosterically activated. It also signals extracellularly via glutamate receptors (AMPA and NMDA receptors) to modulate glucagon, insulin and somatostatin secretion, and islet cell survival....

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Diabetes: Incretin pathway regulates β-cell survival

Tue, 29 Dec 2015 00:00:00 +0100

Nature Reviews Endocrinology 12, 64 (2016). doi:10.1038/nrendo.2015.231 Author: Robert Phillips Newly published data have shown that the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) promotes β-cell function and survival via regulation of TCF7 expression. This mechanism is distinct from that of glucagon-like peptide-1 (GLP-1), and highlights the potential therapeutic benefits of dual incretin agonism.Incretins (Source: Nature Reviews Endocrinology)



Exciting Times for Pancreatic Islets: Glutamate Signaling in Endocrine Cells.

Mon, 28 Dec 2015 00:00:00 +0100

Authors: Otter S, Lammert E Abstract Glutamate represents a key excitatory neurotransmitter in the central nervous system, and also modulates the function and viability of endocrine cells in pancreatic islets. In insulin-secreting beta cells, glutamate acts as an intracellular messenger, and its transport into secretory granules promotes glucose- and incretin-stimulated insulin secretion. Mitochondrial degradation of glutamate also contributes to insulin release when glutamate dehydrogenase is allosterically activated. It also signals extracellularly via glutamate receptors (AMPA and NMDA receptors) to modulate glucagon, insulin and somatostatin secretion, and islet cell survival. Its degradation products, GABA and γ-hydroxybutyrate, are released and also influence islet cell beha...



Blockade of Cannabinoid 1 Receptor Improves GLP-1R Mediated Insulin Secretion in Mice

Fri, 25 Dec 2015 00:00:00 +0100

Publication date: Available online 25 December 2015 Source:Molecular and Cellular Endocrinology Author(s): Isabel González-Mariscal, Susan M. Krzysik-Walker, Wook Kim, Michael Rouse, Josephine M. Egan The cannabinoid 1 receptor (CB1) is an important regulator of energy metabolism. Reports of in vivo and in vitro studies give conflicting results regarding its role in insulin secretion, possibly due to circulatory factors, such as incretins. We hypothesized that this receptor may be a regulator of the entero-insular axis. We found that despite lower food consumption and lower body weight postprandial GLP-1 plasma concentrations were increased in CB1 -/- mice compared to CB1 +/+ mice administered a standard diet or high fat/sugar diet. Upon exogenous GLP-1 treatment, CB1 -/- mice had ...



The two pore channel TPC2 is dispensable in pancreatic β-cells for normal Ca(2+) dynamics and insulin secretion.

Wed, 23 Dec 2015 00:00:00 +0100

Authors: Cane MC, Parrington J, Rorsman P, Galione A, Rutter GA Abstract Ca(2+) signals are central to the stimulation of insulin secretion from pancreatic β-cells by glucose and other agents, including glucagon-like peptide-1 (GLP-1). Whilst Ca(2+) influx through voltage-gated Ca(2+) channels on the plasma membrane is a key trigger for glucose-stimulated secretion, mobilisation of Ca(2+) from acidic stores has been implicated in the control of more localised Ca(2+) changes and membrane potential. Nicotinic acid adenine dinucleotide phosphate (NAADP), generated in β-cells in response to high glucose, is a potent mobiliser of these stores, and has been proposed to act through two pore channels (TPC1 and TPC2, murine gene names Tpcn1 and Tpcn2). Whilst the role of TPC1 in the contr...



Knockdown of GLP-1 Receptors in Vagal Afferents Affects Normal Food Intake and Glycemia

Tue, 22 Dec 2015 00:00:00 +0100

Nutrient stimulation of enteroendocrine L cells induces the release of the incretin and satiating peptide glucagon-like peptide 1 (GLP-1). The vagus nerve innervates visceral organs and may contribute to the mediation of gut-derived GLP-1’s effects on food intake, energy homeostasis, and glycemic control. To test the hypothesis that vagal afferent neuron (VAN) GLP-1 receptors (GLP-1Rs) are necessary for these effects of endogenous GLP-1, we established a novel bilateral nodose ganglia injection technique to deliver a lentiviral vector and to knock down VAN GLP-1Rs in male Sprague Dawley rats. We found that a full expression of VAN GLP-1Rs is not necessary for the maintenance of long-term energy balance in normal eating conditions. VAN GLP-1R knockdown (kd) did, however, increase meal...

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Glucose-Dependent Insulinotropic Polypeptide Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB

Tue, 22 Dec 2015 00:00:00 +0100

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the proatherogenic cytokine osteopontin (OPN) in mouse arteries via local release of endothelin-1 and activation of CREB. Infusion of GIP increases plasma OPN concentrations in healthy individuals. Plasma endothelin-1 and OPN concentrations are positively correlated in patients with critical limb ischemia. Fasting GIP concentrations are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared with control subjects. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients wi...



Weight Loss Decreases Excess Pancreatic Triacylglycerol Specifically in Type 2 Diabetes

Tue, 22 Dec 2015 00:00:00 +0100

CONCLUSIONS The fall in intrapancreatic triacylglycerol in T2DM, which occurs during weight loss, is associated with the condition itself rather than decreased total body fat. (Source: Diabetes Care)



Liraglutide Versus Exenatide Once Weekly: Persistence, Adherence, and Early Discontinuation.

Wed, 16 Dec 2015 00:00:00 +0100

This study examines real-world, evidence-based comparisons of persistence and adherence to daily versus weekly glucagon-like peptide 1 (GLP-1) receptor agonists for the treatment of type 2 diabetes (T2D). METHODS: This retrospective observational study used U.S. insurance claims data to compare persistence and adherence to GLP-1 receptor agonists in patients with T2D initiating once weekly (QW) exenatide or daily liraglutide over a 6-month follow-up period. Eligible patients had ≥2 diagnoses of T2D, were 18 years of age or older, initiated a new prescription of either the index drug between February 1, 2012 (market availability launch date of exenatide QW) and March 31, 2013, and had ≥6 months continuous eligibility in the pre- and postindex periods. A 1:1 propensity score match w...



Novel GLP-1 (Glucagon-Like Peptide-1) Analogues and Insulin in the Treatment for Alzheimer’s Disease and Other Neurodegenerative Diseases

Mon, 14 Dec 2015 00:00:00 +0100

Abstract The link between diabetes mellitus and Alzheimer’s disease (AD) has been known for the last few decades. Since insulin and insulin receptors are known to be present in the brain, the downstream signalling as well as the effect of hyperinsulinemia have been extensively studied in both AD and Parkinson’s disease. Glucagon-like peptide-1 (GLP-1) is a hormone belonging to the incretin family, and its receptors (GLP-1Rs) can be found in pancreatic cells and in vascular endothelium. Interestingly, GLP-1Rs are found in the neuronal cell body and dendrites in the central nervous system (CNS), in particular in the hypothalamus, hippocampus, cerebral cortex and olfactory bulb. Several studies have shown the importance of both insulin and GLP-1 signalling on cognitive functi...



Incretin hormones and maturity onset diabetes of the young--pathophysiological implications and anti-diabetic treatment potential.

Sat, 12 Dec 2015 20:02:14 +0100

In conclusion, patients with GCK-diabetes show normal incretin and glucagon physiology, thus resembling healthy individuals, in spite of fasting hyperglycaemia and subtle glucose intolerance. In contrast, patients with HNF1A-diabetes exhibited noticeable glucose intolerance, beta cell dysfunction, impaired incretin effect, and inappropriate glucagon response to oral stimuli, hence resembling patients with type 2 diabetes. However, normal responses of incretin hormones and normal insulin sensitivity were found in patients with HNF1A-diabetes. Six weeks of treatment with glimepiride or liraglutide demonstrated glucose lowering effects. This effect was greater with glimepiride, although insignificant, but at the expense of a higher risk of hypoglycaemia (predominantly mild). GLP-1RAs may have...

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Patient tolerance and acceptance of colesevelam hydrochloride: focus on type-2 diabetes mellitus.

Sat, 12 Dec 2015 17:05:33 +0100

Authors: Brunetti L, DeSantis EH Abstract Diabetes mellitus (DM) is a chronic disease with a U.S. prevalence of 25.8 million, and 90-95% of all cases are type-2 diabetes mellitus (T2DM). Despite the known mortality and morbidity associated with T2DM, the majority of patients do not achieve their hemoglobin A1c (HbA1c) goals. Nonadherence is one of the contributing factors to the lackluster attainment of treatment goals. Drug tolerability may impact medication nonadherence; therefore, strategies to improve tolerability are important. Colesevelam, a second-generation bile acid resin, was designed with greater specificity and affinity for bile acids. Its physiochemical attributes contribute to an improved tolerability profile. Colesevelam has demonstrated efficacy in lowering HbA1c in...



Laparoscopic gastric plication and its effect on saccharide and lipid metabolism: a 12-month prospective study.

Fri, 11 Dec 2015 03:56:05 +0100

CONCLUSIONS: Laparoscopic greater curvature plication appears to be a procedure with good restriction results, which might be mediated through alteration in incretin metabolism. Technical aspects and standardization of the procedure still remain to be worked out. PMID: 26649086 [PubMed - as supplied by publisher] (Source: Videosurgery and Other Miniinvasive Techniques)



Equine hyperinsulinemia: investigation of the enteroinsular axis during insulin dysregulation

Wed, 09 Dec 2015 00:00:00 +0100

This study investigated peripheral and gut-derived factors impacting insulin secretion by comparing the response to intravenous (iv) and oral d-glucose. Oral and iv tests were performed in 22 ponies previously shown to be insulin dysregulated, of which only 15 were classified as IR (iv test). In a more detailed study, nine different ponies received four treatments: d-glucose orally, d-glucose iv, oats, and commercial grain mix. Insulin, glucose, and incretin concentrations were measured before and after each treatment. All nine ponies showed similar iv responses, but five were markedly hyperresponsive to oral d-glucose and four were not. Insulin responsiveness to oral d-glucose was strongly associated with blood glucose concentrations and oral glucose bioavailability, presumably driven by ...



High-fat diet and palmitate alter the rhythmic secretion of glucagon-like peptide-1 by the rodent L-cell.

Tue, 08 Dec 2015 00:00:00 +0100

Authors: Gil-Lozano M, Wu WK, Martchenko A, Brubaker PL Abstract Secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1), by the intestinal L-cell is rhythmically regulated by an independent molecular clock. However, the impact of factors known to affect the activity of similar cell-autonomous clocks, such as circulating glucocorticoids and high-fat feeding, on GLP-1 secretory patterns remains to be elucidated. Herein, the role of the endogenous corticosterone rhythm on the pattern of GLP-1 and insulin nutrient-induced responses was examined in corticosterone pellet-implanted rats. Moreover, the impact of nutrient excess on the time-dependent secretion of both hormones was assessed in rats fed a high-fat, high-sucrose diet. Finally, the effects of the saturated fatty aci...



Effects of intraduodenal hydroxycitrate on glucose absorption, incretin release and glycemia in response to intraduodenal glucose infusion in health and type 2 diabetes – a randomised controlled trial (NUT-D-15-00649 revised version)

Mon, 07 Dec 2015 00:00:00 +0100

Hydroxycitric acid (HCA), derived from the fruit Garcinia cambogia, reduces the rate of glucose absorption and lowers postprandial glycemia in rodents, but its effect in humans is unknown. (Source: Nutrition)

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Effects of intraduodenal hydroxycitrate on glucose absorption, incretin release, and glycemia in response to intraduodenal glucose infusion in health and type 2 diabetes: A randomised controlled trial

Mon, 07 Dec 2015 00:00:00 +0100

Hydroxycitric acid (HCA), derived from the fruit Garcinia cambogia, reduces the rate of glucose absorption and lowers postprandial glycemia in rodents, but its effect in humans is unknown. The aim of this study was to investigate the effects of small intestinal perfusion with HCA on glucose absorption, as well as the incretin and glycemic responses to a subsequent intraduodenal glucose infusion, in both healthy individuals and patients with type 2 diabetes. (Source: Nutrition)



Drugs for type 2 diabetes: role in the regulation of bone metabolism.

Wed, 02 Dec 2015 05:00:57 +0100

Authors: Mannucci E, Dicembrini I Abstract Until a few years ago, the possibility that glucose-lowering drugs affect glucose metabolism and fracture risk was not even considered. The increased incidence of fractures with thiazolidinediones in women was a causal finding. This phenomenon, which has been demonstrated by large-scale clinical trials, is associated with a reduction in bone density. Thiazolidinediones stimulate adipocyte differentiation, and inhibit osteoblast differentiation, from bone marrow stromal cells; other mechanisms could also be involved in the thiazolidinedione-induced reduction of bone density. Insulin has an anabolic effect on the bone, but it is nonetheless associated with an increased incidence of fractures in observational studies. Although this finding co...



Comparative effects of intraduodenal whey protein hydrolysate on antropyloroduodenal motility, gut hormones, glycemia, appetite, and energy intake in lean and obese men [Obesity and eating disorders]

Tue, 01 Dec 2015 00:00:00 +0100

Conclusions: The gastrointestinal effects of hydrolyzed whey protein remain relatively intact in obesity; however, the observed changes in insulin and GIP suggest early disturbances in the insulin–incretin axis. This study was registered at www.anzctr.org.au as ACTRN 12612000203853. (Source: American Journal of Clinical Nutrition)



GLP-1 Mimetic Drugs and the risk of Exocrine Pancreatic disease: Cell and Animal Studies

Tue, 01 Dec 2015 00:00:00 +0100

Glucagon Like Peptide 1 (GLP-1) mimetic drugs or degradation inhibitors mimic the action of native GLP-1 as a incretin hormone and have become a common second line of therapy for Type 2 diabetes. However, an important clinical issue is whether these drugs increase the incidence of pancreatitis and pancreatic cancer. (Source: Pancreatology)



Galanin inhibits GLP‐1 and GIP secretion via the GAL1 receptor in enteroendocrine L and K cells

Tue, 01 Dec 2015 00:00:00 +0100

Conclusions and ImplicationsGalanin, acting via the GAL1 receptor and Gi‐coupled signalling in L and K cells, is a potent inhibitor of GLP‐1 and GIP secretion. Although GIRK1/4 channels are expressed in these cells, their activation does not appear to play a major role in galanin‐mediated inhibition of incretin secretion. This article is protected by copyright. All rights reserved. (Source: British Journal of Pharmacology)

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Incretins, Diabetes, Pancreatitis and Pancreatic Cancer: What the GI specialist needs to know

Tue, 01 Dec 2015 00:00:00 +0100

There has been recent concern over the pancreatic safety of incretin-based therapies for diabetes. While drug-induced pancreatitis is a rare event, the large number of patients with diabetes make the potential impact of diabetic drugs significant. This review examines the relationship between diabetes, pancreatitis, and pancreatic cancer and the data assessing the potential impact of incretin-based therapies on these diseases. (Source: Pancreatology)



Incretin effects, gastric emptying and insulin responses to low oral glucose loads in patients after gastric bypass and lean and obese controls

Fri, 27 Nov 2015 00:00:00 +0100

After gastric bypass (LRYGB) many patients suffer from dumping syndrome. Oral glucose tolerance tests are usually carried out with 50-75g of glucose. The aim of this study was to examine whether minimal glucose loads of 10g and 25g induce a reliable secretion of satiation peptides without dumping symptoms after LRYGB. In addition, lean and obese controls were examined. (Source: Surgery for Obesity and Related Diseases)



Cardiovascular Outcomes of Dipeptidyl Peptidase-4 Inhibitors in Elderly Patients With Type 2 Diabetes: A Nationwide Study

Fri, 20 Nov 2015 00:00:00 +0100

The elderly (aged ≥65 years) population with type 2 diabetes (T2D) is growing substantially, but evidence for associations between the use of dipeptidyl peptidase-4 inhibitors (DPP-4is), novel incretin-based antidiabetic drugs, and clinical hard endpoints in this group remains inconclusive. We aimed to assess the safety and cardiovascular effects of DPP-4i use in a nationally representative sample of elderly adults with T2D. (Source: Journal of the American Medical Directors Association)



GLP1- and GIP-producing cells rarely overlap and differ by bombesin receptor-2 expression and responsiveness

Fri, 20 Nov 2015 00:00:00 +0100

The incretin hormones glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from intestinal endocrine cells, the so-called L- and K-cells. The cells are derived from a common precursor and are highly related, and co-expression of the two hormones in so-called L/K-cells has been reported. To investigate the relationship between the GLP1- and GIP-producing cells more closely, we generated a transgenic mouse model expressing a fluorescent marker in GIP-positive cells. In combination with a mouse strain with fluorescent GLP1 cells, we were able to estimate the overlap between the two cell types. Furthermore, we used primary cultured intestinal cells and isolated perfused mouse intestine to measure the secretion of GIP and GLP1 in response to differe...



Incretin-like effects of small molecule trace amine-associated receptor 1 agonists

Thu, 19 Nov 2015 00:00:00 +0100

Conclusions We have identified TAAR1 as a novel integrator of metabolic control, which acts on gastrointestinal and pancreatic islet hormone secretion. Thus TAAR1 qualifies as a novel and promising target for the treatment of type 2 diabetes and obesity. Graphical abstract (Source: Molecular Metabolism)

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Cardiovascular, renal and gastrointestinal effects of incretin-based therapies: an acute and 12-week randomised, double-blind, placebo-controlled, mechanistic intervention trial in type 2 diabetes

Thu, 19 Nov 2015 00:00:00 +0100

Introduction Incretin-based therapies, that is, glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors, are relatively novel antihyperglycaemic drugs that are frequently used in type 2 diabetes management. Apart from glucose-lowering, these agents exhibit pleiotropic actions that may have favourable and unfavourable clinical consequences. Incretin-based therapies have been associated with heart rate acceleration, heart failure, acute renal failure and acute pancreatitis. Conversely, these agents may reduce blood pressure, glomerular hyperfiltration, albuminuria and hepatic steatosis. While large-sized cardiovascular safety trials can potentially identify the clinical significance of some of these pleiotropic actions, small-sized mechanistic studies are ...



Weight Loss as a Cure for Type 2 Diabetes? Fact or Fantasy.

Wed, 18 Nov 2015 17:31:21 +0100

Authors: Kashyap SR, Louis ES, Kirwan JP Abstract Although individuals with obesity and type 2 diabetes are insulin resistant, pancreatic beta cell failure is the core defect that distinguishes individuals who eventually develop diabetes. This process is known to occur well before the onset of hyperglycemia. Although clinical trial data support the effectiveness of intensive lifestyle modification in delaying the onset of diabetes in obese subjects, less is known about the effects of and mechanisms underlying bariatric surgery, particularly gastric bypass surgery, on diabetes. The paper under evaluation clarifies the role of both lifestyle intervention and gastric bypass surgery on pancreatic beta cell function and raises questions regarding the role of weight loss versus incretin ...