14,585 results match your criteria incretin secretion


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Mol Pharmacol 2021 Jul 27. Epub 2021 Jul 27.

Imperial College London, United Kingdom

The glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor and mainstay therapeutic target for the treatment of type 2 diabetes and obesity. Recent reports have highlighted how biased agonism at the GLP-1R affects sustained glucose-stimulated insulin secretion through avoidance of desensitisation and downregulation. A number of GLP-1R agonists (GLP-1RAs) feature a fatty acid moiety to prolong their pharmacokinetics via increased albumin binding, but the potential for these chemical changes to influence GLP-1R function has rarely been investigated beyond potency assessments for cyclic adenosine monophosphate (cAMP). Read More

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Heterogeneity amongst GLP-1 RA cardiovascular outcome trials results: can definition of established cardiovascular disease be the missing link?

Diabetol Metab Syndr 2021 Jul 27;13(1):81. Epub 2021 Jul 27.

Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar E Universitário S. João, Porto, Portugal.

Atherosclerotic cardiovascular diseases are the leading cause of adverse outcomes in patients with type 2 diabetes, and all new anti-diabetic agents are mandated to undergo cardiovascular outcome trials (CVOTs). Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are incretin mimetics that reduce blood glucose levels with a low associated risk of hypoglycaemia. CVOTs with different GLP-1 RAs yielded different results in terms of major cardiovascular composite outcome (MACE), with some trials showing superiority in the treatment arm, whereas other simply displayed non-inferiority. Read More

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The Evolving Story of Incretins (GIP and GLP-1) in Metabolic and Cardiovascular Disease: A Pathophysiological Update.

Diabetes Obes Metab 2021 Jul 26. Epub 2021 Jul 26.

Charité - Universitätsmedizin Berlin, Klinik für Endokrinologie, Stoffwechsel- und Ernährungsmedizin, Berlin, Germany.

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have their main physiological role in augmenting insulin secretion after their nutrient-induced secretion from the gut. A functioning entero-insular (gut-endocrine pancreas) axis is essential for the maintenance of a normal glucose tolerance. This is exemplified by the incretin effect (greater insulin secretory response to oral as compared to "isoglycaemic" intravenous glucose administration due to the secretion and action of incretin hormones). Read More

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[Exendin-4 promotes autophagy to relieve lipid deposition in a NAFLD cell model by activating AKT/mTOR signaling pathway].

Nan Fang Yi Ke Da Xue Xue Bao 2021 Jul;41(7):1073-1078

Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.

Objective: To investigate the effect of exendin-4 on lipid deposition in hepatocytes and explore its possible mechanism for treatment of nonalcoholic fatty liver disease (NAFLD).

Methods: Human normal hepatocyte line LO2 and hepatoma cell line HepG2 were treated with palmitic acid (PA) to mimic hepatocyte steatosis or with combined treatments with PA+exendin-4 or PA+exendin-4+3BDO. Lipid deposition and proliferation of the two cell lines following treatment with PA or PA+exendin-4 were detected using Oil Red O staining and CCK8 assay, and the expression of p-mTOR, m-TOR, p-AKT, AKT and autophagy-related proteins LC3-Ⅰ/Ⅱ and p62 were detected with Western blotting; the expression of GLP-1R was detected with both Western blotting and immunofluorescence assay. Read More

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The Role of Positron Emission Tomography in Bariatric Surgery Research: a Review.

Obes Surg 2021 Jul 25. Epub 2021 Jul 25.

Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.

Bariatric surgery, initially understood as restricting or bypassing the amount of food that reaches the stomach to reduce food intake and/or increase malabsorption of food to promote weight loss, is now recognized to also affect incretin signaling in the gut and promote improvements in system-wide metabolism. Positron emission tomography (PET) is an imaging technique whereby patients are injected with picomolar concentrations of radioactive molecules, below the threshold of having physiological effects, to measure spatial distributions of blood flow, metabolism, receptor, and enzyme pharmacology. Recent advances in both whole-body PET imaging and radioligand development will allow for novel research that may help clarify the roles of peripheral and central receptor/enzyme systems in treating obesity with bariatric surgery. Read More

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An Autonomous Cannabinoid System in Islets of Langerhans.

Front Endocrinol (Lausanne) 2021 5;12:699661. Epub 2021 Jul 5.

Laboratory of Clinical Investigation/Diabetes Section, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States.

While endocannabinoids (ECs) and cannabis were primarily studied for their nervous system effects, it is now clear that ECs are also produced in the periphery where they regulate several physiological processes, including energy storage, glucose and lipid metabolism, insulin secretion and synthesis, and hepatocyte function. Within islet of Langerhans there is an autonomous EC system (ECS). Beta (β)-cells contain all the enzymes necessary for EC synthesis and degradation; ECs are generated in response to cellular depolarization; their paracrine influence on β-cells is mostly through the cannabinoid 1 receptor (CBR) that is present on all β-cells; they modulate basal and glucose- and incretin-induced insulin secretion, and β-cell responses to various stressors. Read More

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Attenuated Postprandial GLP-1 Response in Parkinson's Disease.

Front Neurosci 2021 2;15:660942. Epub 2021 Jul 2.

Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States.

The incretin hormone glucagon-like peptide 1 (GLP-1) has neuroprotective effects in animal models of Parkinson's disease (PD), and GLP-1 receptor agonists are associated with clinical improvements in human PD patients. GLP-1 is produced and secreted by intestinal L-cells in response to consumption of a meal. Specifically, intestinal microbiota produce short chain fatty acids (SCFA) which, in turn, promote secretion of GLP-1 into the systemic circulation, from which it can enter the brain. Read More

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The effect of melatonin on incretin hormones - results from experimental and randomized clinical studies.

J Clin Endocrinol Metab 2021 Jul 15. Epub 2021 Jul 15.

Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.

Context: Glucose homeostasis is under circadian control through both endocrine and intracellular mechanisms with several lines of evidence suggesting that melatonin affects glucose homeostasis.

Objective: To evaluate the acute in-vivo and in-situ effects of melatonin on secretion of the incretin hormones, GLP-1 and GIP, and their impact on β-cell insulin secretion.

Design: A human randomized, double-blinded, placebo-controlled crossover study combined with a confirmatory in-situ study of perfused rat intestines. Read More

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The enteroendocrine-osseous axis in patients with long-term type 1 diabetes mellitus.

Bone 2021 Jul 8;153:116105. Epub 2021 Jul 8.

Department of Pediatric and Adolescent Endocrinology, Pediatric Institute, Jagiellonian University Medical College, Kraków, Poland. Electronic address:

Introduction: The relationship between the gut and skeleton is increasingly recognized as a component of the regulation of carbohydrate metabolism. The aim of our study was to assess the relationship between bone mineral density (BMD), incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), intestinotrophic peptide glucagon-like peptide-2 (GLP-2) and osteocalcin isoforms in patients with long-term type 1 diabetes (T1D) when compared to healthy controls.

Methods: Eighty two patients with long term T1D, treated in the Department of Metabolic Diseases and 53 healthy controls were recruited to the study. Read More

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Actions of GLP-1 receptor ligands in the gut.

Br J Pharmacol 2021 Jul 7. Epub 2021 Jul 7.

Department of Biomedical Sciences and NovoNordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen.

The incretin hormone glucagon-like peptide-1 (GLP-1) is inactivated by the enzyme DPP-4 even before it leaves the gut but seems to act predominantly via activation of intestinal sensory neurons expressing the GLP-1 receptor. Thus activation of vagal afferents is probably responsible for its effects on appetite and food intake, gastrointestinal secretion and motility, and pancreatic endocrine secretion. However, GLP-1 receptors are widely expressed in the gastrointestinal tract, including epithelial cells in the stomach, and the Brunner glands, in endocrine cells of the gut epithelium, and on mucosal lymphocytes. Read More

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Targeting the GPR119/incretin axis: a promising new therapy for metabolic-associated fatty liver disease.

Cell Mol Biol Lett 2021 Jul 7;26(1):32. Epub 2021 Jul 7.

Institute of Liver Diseases, Shuguang Hospital Affiliated To Shanghai, University of Traditional Chinese Medicine, 528, Zhangheng Road, Shanghai, China.

In the past decade, G protein-coupled receptors have emerged as drug targets, and their physiological and pathological effects have been extensively studied. Among these receptors, GPR119 is expressed in multiple organs, including the liver. It can be activated by a variety of endogenous and exogenous ligands. Read More

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The Postprandial Glycaemic and Hormonal Responses Following the Ingestion of a Novel, Ready-to-Drink Shot Containing a Low Dose of Whey Protein in Centrally Obese and Lean Adult Males: A Randomised Controlled Trial.

Front Endocrinol (Lausanne) 2021 18;12:696977. Epub 2021 Jun 18.

Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.

Purpose: Elevated postprandial glycaemia [PPG] increases the risk of cardiometabolic complications in insulin-resistant, centrally obese individuals. Therefore, strategies that improve PPG are of importance for this population. Consuming large doses of whey protein [WP] before meals reduces PPG by delaying gastric emptying and stimulating the secretion of the incretin peptides, glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide 1 [GLP-1]. Read More

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Sex differences in oxidative stress level and antioxidative enzymes expression and activity in obese pre-diabetic elderly rats treated with metformin or liraglutide.

Croat Med J 2021 Jun;62(3):215-226

Ines Drenjančević, Institute and Department of Physiology and Immunology, Faculty of Medicine University Josip Juraj Strossmayer of Osijek, J. Huttlera 4, 31 000 Osijek, Croatia,

Aim: To determine the effects of metformin or liraglutide on oxidative stress level and antioxidative enzymes gene expression and activity in the blood and vessels of pre-diabetic obese elderly Sprague-Dawley (SD) rats of both sexes.

Methods: Male and female SD rats were assigned to the following groups: a) control group (fed with standard rodent chow); b) high-fat and high-carbohydrate diet (HSHFD) group fed with HSHFD from 20-65 weeks of age; c) HSHFD+metformin treatment (50 mg/kg/d s.c. Read More

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A 2021 Update on the Use of Liraglutide in the Modern Treatment of 'Diabesity': A Narrative Review.

Medicina (Kaunas) 2021 Jun 29;57(7). Epub 2021 Jun 29.

Department ME2, Faculty of Medicine, "George Emil Palade" University of Medicine, Pharmacy, Science and Technology, 540136 Targu Mures, Romania.

Obesity and type 2 diabetes mellitus have become a significant public health problem in the past decades. Their prevalence is increasing worldwide each year, greatly impacting the economic and personal aspects, mainly because they frequently coexist, where the term "diabesity" may be used. The drug class of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) is one of the most modern therapy options in managing these metabolic disorders. Read More

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Dipeptidyl Peptidase (DPP)-IV Inhibitors with Antioxidant Potential Isolated from Natural Sources: A Novel Approach for the Management of Diabetes.

Pharmaceuticals (Basel) 2021 Jun 18;14(6). Epub 2021 Jun 18.

Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Korea.

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia that is predominantly caused by insulin resistance or impaired insulin secretion, along with disturbances in carbohydrate, fat and protein metabolism. Various therapeutic approaches have been used to treat diabetes, including improvement of insulin sensitivity, inhibition of gluconeogenesis, and decreasing glucose absorption from the intestines. Recently, a novel approach has emerged using dipeptidyl peptidase-IV (DPP-IV) inhibitors as a possible agent for the treatment of T2DM without producing any side effects, such as hypoglycemia and exhaustion of pancreatic β-cells. Read More

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The Capacity to Secrete Insulin Is Dose-Dependent to Extremely High Glucose Concentrations: A Key Role for Adenylyl Cyclase.

Metabolites 2021 Jun 19;11(6). Epub 2021 Jun 19.

Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA.

Insulin secretion is widely thought to be maximally stimulated in glucose concentrations of 16.7-to-30 mM (300-to-540 mg/dL). However, insulin secretion is seldom tested in hyperglycemia exceeding these levels despite the Guinness World Record being 147. Read More

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Effects of Incretin-Related Diabetes Drugs on Bone Formation and Bone Resorption.

Int J Mol Sci 2021 Jun 19;22(12). Epub 2021 Jun 19.

Division of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Tohoku University, 4-1, Seiryo-machi, Aoba-ku, Miyagi, Sendai 980-8575, Japan.

Patients with type 2 diabetes have an increased risk of fracture compared to the general population. Glucose absorption is accelerated by incretin hormones, which induce insulin secretion from the pancreas. The level of the incretin hormone, glucagon-like peptide-1 (GLP-1), shows an immediate postprandial increase, and the circulating level of intact GLP-1 is reduced rapidly by dipeptidyl peptidase-4 (DPP-4)-mediated inactivation. Read More

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The Change in Glucagon Following Meal Ingestion Is Associated with Glycemic Control, but Not with Incretin, in People with Diabetes.

J Clin Med 2021 Jun 4;10(11). Epub 2021 Jun 4.

Department of Internal Medicine, College of Medicine, Jeju National University, Jeju 63241, Korea.

Background: We aimed to investigate the changes in glucagon levels in people with diabetes after the ingestion of a mixed meal and the correlations of variation in glucagon levels with incretin and clinico-biochemical characteristics.

Methods: Glucose, C-peptide, glucagon, intact glucagon-like peptide 1 (iGLP-1), and intact glucose-dependent insulinotropic polypeptide (iGIP) were measured in blood samples collected from 317 people with diabetes before and 30 min after the ingestion of a standard mixed meal. The delta (Δ) is the 30-min value minus the basal value. Read More

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New Aspects of Diabetes Research and Therapeutic Development.

Pharmacol Rev 2021 Jul;73(3):1001-1015

Department of Pharmacology (L.S.S.), Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine (L.S.S., S.A.S., E.M.W.), and Brehm Diabetes Center (L.S.S., S.A.S., E.M.W.), University of Michigan Medical School, Ann Arbor, Michigan; and VA Ann Arbor Healthcare System, Ann Arbor, Michigan (S.A.S.)

Both type 1 and type 2 diabetes mellitus are advancing at exponential rates, placing significant burdens on health care networks worldwide. Although traditional pharmacologic therapies such as insulin and oral antidiabetic stalwarts like metformin and the sulfonylureas continue to be used, newer drugs are now on the market targeting novel blood glucose-lowering pathways. Furthermore, exciting new developments in the understanding of beta cell and islet biology are driving the potential for treatments targeting incretin action, islet transplantation with new methods for immunologic protection, and the generation of functional beta cells from stem cells. Read More

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Protein- and Calcium-Mediated GLP-1 Secretion: A Narrative Review.

Adv Nutr 2021 Jun 30. Epub 2021 Jun 30.

Centre for Nutrition, Exercise and Metabolism, Department for Health, University of Bath, Bath, United Kingdom.

Glucagon-like peptide 1 (GLP-1) is an incretin hormone produced in the intestine that is secreted in response to nutrient exposure. GLP-1 potentiates glucose-dependent insulin secretion from the pancreatic β cells and promotes satiety. These important actions on glucose metabolism and appetite have led to widespread interest in GLP-1 receptor agonism. Read More

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Tirzepatide and the new era of twincretins for diabetes.

Lancet 2021 07 27;398(10295):95-97. Epub 2021 Jun 27.

Endocrinology, Division of Medicine, University College London, Royal Free Campus, London, UK.

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Effect of Fecal Microbiota Transplantation Combined With Mediterranean Diet on Insulin Sensitivity in Subjects With Metabolic Syndrome.

Front Microbiol 2021 10;12:662159. Epub 2021 Jun 10.

Department of Internal Medicine and (Experimental) Vascular Medicine, Amsterdam University Medical Center, Location Academic Medical Center, Amsterdam, Netherlands.

Background: Recent studies demonstrate that a Mediterranean diet has beneficial metabolic effects in metabolic syndrome subjects. Since we have shown that fecal microbiota transplantation (FMT) from lean donors exerts beneficial effects on insulin sensitivity, in the present trial, we investigated the potential synergistic effects on insulin sensitivity of combining a Mediterranean diet with donor FMT in subjects with metabolic syndrome.

Design: Twenty-four male subjects with metabolic syndrome were put on a Mediterranean diet and after a 2-week run-in phase, the subjects were randomized to either lean donor ( = 12) or autologous ( = 12) FMT. Read More

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Single-Cell Mapping of GLP-1 and GIP Receptor Expression in the Dorsal Vagal Complex.

Diabetes 2021 Jun 27. Epub 2021 Jun 27.

Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark

The dorsal vagal complex (DVC) in the hindbrain, composed of the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus, plays a critical role in modulating satiety. The incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) act directly in the brain to modulate feeding, and receptors for both are expressed in the DVC. Given the impressive clinical responses to pharmacologic manipulation of incretin signaling, understanding the central mechanisms by which incretins alter metabolism and energy balance is of critical importance. Read More

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Effects of efpeglenatide versus liraglutide on gastric emptying, glucose metabolism and beta-cell function in people with type 2 diabetes: an exploratory, randomized phase Ib study.

BMJ Open Diabetes Res Care 2021 06;9(1)

Clinical Investigation, ProSciento Inc, Chula Vista, California, USA.

Introduction: To evaluate the effects of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), on gastric emptying, glucose metabolism, and islet beta-cell function versus liraglutide and placebo in people with type 2 diabetes.

Research Design And Methods: This phase Ib study (ClinicalTrials.gov identifier: NCT02059564) randomized participants (n=47) to three cohorts. Read More

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Impact of Incretin Hormone Receptors on Insulin-Independent Glucose Disposal in Model Experiments in Mice.

Front Endocrinol (Lausanne) 2021 8;12:680153. Epub 2021 Jun 8.

Department of Clinical Sciences Lund, Lund University, Lund, Sweden.

A large contribution to glucose elimination from the circulation is achieved by insulin-independent processes. We have previously shown that the two incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) increase this process and, therefore, seem to contribute to glucose disposal both through this effect and through the classical incretin effect resulting in enhanced insulin levels. We have now explored in more detail the potential contribution by incretin hormone receptors to insulin-independent processes for glucose elimination. Read More

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Activation of AMPK/mTOR-driven autophagy and inhibition of NLRP3 inflammasome by saxagliptin ameliorate ethanol-induced gastric mucosal damage.

Life Sci 2021 Sep 21;280:119743. Epub 2021 Jun 21.

Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt.

Aims: Saxagliptin, a selective/potent dipeptidyl peptidase-4 inhibitor, has revealed remarkable anti-inflammatory features in murine models of nephrotoxicity, hepatic injury, and neuroinflammation. However, its potential effect on ethanol-induced gastric mucosal injury has not been examined. Hence, the present work investigated the prospect of saxagliptin to attenuate ethanol-evoked gastric injury, with emphasis on the AMPK/mTOR-driven autophagy and NLRP3/ASC/caspase-1 pathway. Read More

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September 2021

Erectile function in men with type 2 diabetes treated with dulaglutide: an exploratory analysis of the REWIND placebo-controlled randomised trial.

Lancet Diabetes Endocrinol 2021 Aug 18;9(8):484-490. Epub 2021 Jun 18.

St John's Medical College, St John's National Academy of Health Sciences, Bangalore, India.

Background: Diabetes is a major risk factor for erectile dysfunction, however, the effect of GLP-1 receptor agonists on erectile dysfunction is unknown. We aimed to assess the incidence, prevalence, and progression of erectile dysfunction in men treated with dulaglutide compared with placebo, and to determine whether dulaglutide's effect on erectile dysfunction was consistent with its effect on other diabetes-related outcomes.

Methods: The Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial was a double-blind, placebo-controlled randomised trial of the effect of dulaglutide on cardiovascular outcomes. Read More

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Molecular insights into ago-allosteric modulation of the human glucagon-like peptide-1 receptor.

Nat Commun 2021 06 18;12(1):3763. Epub 2021 Jun 18.

School of Pharmacy, Fudan University, Shanghai, China.

The glucagon-like peptide-1 (GLP-1) receptor is a validated drug target for metabolic disorders. Ago-allosteric modulators are capable of acting both as agonists on their own and as efficacy enhancers of orthosteric ligands. However, the molecular details of ago-allosterism remain elusive. Read More

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Holdemanella biformis improves glucose tolerance and regulates GLP-1 signaling in obese mice.

FASEB J 2021 07;35(7):e21734

Microbial Ecology, Nutrition and Health Research Unit, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Valencia, Spain.

Impaired glucose homeostasis in obesity is mitigated by enhancing the glucoregulatory actions of glucagon-like peptide 1 (GLP-1), and thus, strategies that improve GLP-1 sensitivity and secretion have therapeutic potential for the treatment of type 2 diabetes. This study shows that Holdemanella biformis, isolated from the feces of a metabolically healthy volunteer, ameliorates hyperglycemia, improves oral glucose tolerance and restores gluconeogenesis and insulin signaling in the liver of obese mice. These effects were associated with the ability of H. Read More

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Role of liraglutide in Alzheimer's disease pathology.

Alzheimers Res Ther 2021 06 12;13(1):112. Epub 2021 Jun 12.

Division of Physiology, School of Medicine, Instituto de Investigacion Biomedica de Cadiz (INIBICA), Universidad de Cadiz, Edificio Andres Segovia, C/Dr. Maranon 3, 3er piso, Cadiz, Spain.

Background: The described relationship between Alzheimer's disease (AD) and type 2 diabetes (T2D) and the fact that AD has no succesful treatment has led to the study of antidiabetic drugs that may limit or slow down AD pathology.

Main Body: Although T2D treatment has evident limitations, options are increasing including glucagon-like peptide 1 analogs. Among these, liraglutide (LRGT) is commonly used by T2D patients to improve β cell function and suppress glucagon to restore normoglycaemia. Read More

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