13,918 results match your criteria secretion glp-1


Metformin stimulates intestinal glycolysis and lactate release: A single-dose study of metformin in patients with intrahepatic portosystemic stent.

Clin Pharmacol Ther 2021 Jul 31. Epub 2021 Jul 31.

Steno Diabetes Center Aarhus, Aarhus University Hospital, 8200, Aarhus N, Denmark.

The pharmacodynamic effects of metformin remain elusive, but several lines of evidence suggest a critical role of direct effects in the gastrointestinal (GI) tract. We investigated if metformin stimulates intestinal glucose metabolism and lactate release in the prehepatic circulation. We included eight patients with transjugular intrahepatic portosytemic stent (TIPS) in an open label study. Read More

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NONALCOHOLIC FATTY LIVER DISEASE-RELATED RISK OF CARDIOVASCULAR DISEASE AND OTHER CARDIAC COMPLICATIONS.

Diabetes Obes Metab 2021 Jul 29. Epub 2021 Jul 29.

Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.

Background/aim: Nonalcoholic fatty liver disease (NAFLD) affects approximately ~25% of the global adult population. The aim of this narrative review is to describe the associations between NAFLD and cardiovascular disease (CVD), arrhythmias, cardiac conduction defects, myocardial remodelling and heart failure. We also discuss the potential mechanisms that mediate or attenuate the strength of these associations, and briefly summarize the effect of treatments that both ameliorate NAFLD and decrease risk of CVD. Read More

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SCO-267, a GPR40 Full Agonist, Stimulates Islet and Gut Hormone Secretion and Improves Glycemic Control in Humans.

Diabetes 2021 Jul 28. Epub 2021 Jul 28.

SCOHIA PHARMA Inc., Kanagawa, Japan

SCO-267 is a full agonist of the free fatty acid receptor 1 (GPR40), which regulates the secretion of islet and gut hormones. In this phase 1 study, we aimed to evaluate the clinical profile of single and multiple once-daily oral administration of SCO-267 in healthy adults and patients with diabetes. Plasma SCO-267 concentration was seen to increase in a dose-dependent manner after administration, and its plasma exposure was maintained for 24 h. Read More

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Preproglucagon Products and Their Respective Roles Regulating Insulin Secretion.

Endocrinology 2021 Jul 28. Epub 2021 Jul 28.

Department of Pediatrics, Nutrition Section, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Historically, intracellular function and metabolic adaptation within the α-cell has been understudied, with most of the attention being placed on the insulin-producing β-cells due to their role in the pathophysiology of Type 2 Diabetes Mellitus. However, there is a growing interest in understanding the function of other endocrine cell types within the islet and their paracrine role in regulating insulin secretion. For example, there is greater appreciation for α-cell products and their contributions to overall glucose homeostasis. Read More

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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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CAPTURE: a multinational, cross-sectional study of cardiovascular disease prevalence in adults with type 2 diabetes across 13 countries.

Cardiovasc Diabetol 2021 Jul 27;20(1):154. Epub 2021 Jul 27.

Instituto de Ciencias Farmaceuticas, Goiânia, Goiás, Brazil.

Background: There is a paucity of global data on cardiovascular disease (CVD) prevalence in people with type 2 diabetes (T2D). The primary objective of the CAPTURE study was to estimate the prevalence of established CVD and its management in adults with T2D across 13 countries from five continents. Additional objectives were to further characterize the study sample regarding demographics, clinical parameters and medication usage, with particular reference to blood glucose-lowering agents (GLAs: glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) with demonstrated cardiovascular benefit in randomized intervention trials. Read More

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Efficacy and tolerability of pharmacological interventions on metabolic disturbance induced by atypical antipsychotics in adults: A systematic review and network meta-analysis.

J Psychopharmacol 2021 Jul 27:2698811211035391. Epub 2021 Jul 27.

Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: There have been a few systematic reviews and conventional meta-analyses reporting effect of drugs on metabolic disturbance induced by atypical antipsychotics (AAPs). However, few of them provided sufficient and comprehensive comparisons between pharmacological interventions.

Aims: We aimed to qualitatively compare drugs' effect on AAPs-induced metabolic abnormalities by using network meta-analysis (NMA). 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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Glucagon-Like Peptide 1 Receptor Agonist Usage in Type 2 Diabetes in Primary Care for the UK and Beyond: A Narrative Review.

Diabetes Ther 2021 Jul 26. Epub 2021 Jul 26.

University College London, Royal Free Campus, London, UK.

The scientific landscape of treatments for type 2 diabetes (T2D) has changed rapidly in the last decade with newer treatments becoming available. However, a large proportion of people with T2D are not able to achieve glycaemic goals because of clinical inertia. The majority of T2D management is in primary care, where clinicians (medical, nursing and pharmacist staff) play an important role in addressing patient needs and achieving treatment goals. 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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A quinoxaline-based compound ameliorates bone loss in ovariectomized mice.

Exp Biol Med (Maywood) 2021 Jul 25:15353702211032133. Epub 2021 Jul 25.

Department of Basic Medicine, Xi'an Medical University, Xi'an 710021, PR China.

DMB (6,7-dichloro-2-methylsulfonyl-3-Ntert-butylaminoquinoxaline) is a quinoxaline-based compound that has been investigated as a glucagon-like peptide-1 receptor (GLP-1R) agonist. To clarify anti-osteoporosis effect of DMB, an osteoporotic mice model was established by ovariectomy (OVX) operation. The OVX mice were given intraperitoneally DMB, exendin-4 (EX-4), or 17β-estradiol (E) for two months. Read More

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GLP-1-Induced AMPK Activation Inhibits PARP-1 and Promotes LXR-Mediated ABCA1 Expression to Protect Pancreatic β-Cells Against Cholesterol-Induced Toxicity Through Cholesterol Efflux.

Front Cell Dev Biol 2021 7;9:646113. Epub 2021 Jul 7.

Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, China.

T2DM (Type 2 diabetes) is a complex, chronic disease characterized as insulin resistance and islet β-cell dysfunction. Bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) surgery and laparoscopic sleeve gastrectomy (LSG) have become part of a critical treatment regimen in the treatment of obesity and T2DM. Moreover, GLP-1 increase following bariatric surgery has been regarded as a significant event in bariatric surgery-induced remission of T2DM. Read More

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Glucagon-Like Peptide-1 Receptor Agonist Ameliorates 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Neurotoxicity Through Enhancing Mitophagy Flux and Reducing α-Synuclein and Oxidative Stress.

Front Mol Neurosci 2021 7;14:697440. Epub 2021 Jul 7.

Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Parkinson disease (PD) is the second most common neurodegenerative disease without known disease modification therapy to slow down disease progression. This disease has pathological features of Lewy bodies with α-synuclein aggregation being the major component and selective dopaminergic neuronal loss over the substantia nigra. Although the exact etiology is still unknown, mitochondrial dysfunction has been shown to be central in PD pathophysiology. Read More

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Are the Changes in Gastrointestinal Hormone Secretion Necessary for the Success of Bariatric Surgery? A Critical Review of the Literature.

Obes Surg 2021 Jul 25. Epub 2021 Jul 25.

Division of Bariatric and Metabolic Surgery, Department of Surgery, General University Hospital of Patras, 26504, Rio, Greece.

Ghrelin, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) are involved in energy balance regulation and glucose homeostasis. Obesity is characterized by lower fasting levels and blunted postprandial responses of ghrelin, GLP-1, and possibly PYY. Both Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) have been shown to increase postprandial GLP-1 and PYY levels. Read More

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GLP-2 Is Locally Produced From Human Islets and Balances Inflammation Through an Inter-Islet-Immune Cell Crosstalk.

Front Endocrinol (Lausanne) 2021 5;12:697120. Epub 2021 Jul 5.

Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany.

Glucagon-like peptide-1 (GLP-1) shows robust protective effects on β-cell survival and function and GLP-1 based therapies are successfully applied for type-2 diabetes (T2D) and obesity. Another cleavage product of pro-glucagon, Glucagon-like peptide-2 (GLP-2; both GLP-1 and GLP-2 are inactivated by DPP-4) has received little attention in its action inside pancreatic islets. In this study, we investigated GLP-2 production, GLP-2 receptor (GLP-2R) expression and the effect of GLP-2R activation in human islets. Read More

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Banting Memorial Lecture 2021 Banting, banting, banter and bravado: Convictions meet evidence in the scientific process.

Authors:
Michael Ej Lean

Diabet Med 2021 Jul 20:e14643. Epub 2021 Jul 20.

School of Medicine, Dentistry & Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Scotland.

This personal account presents some glimpses into the clinical research processes which have made radical changes to our understanding of disease and treatment, and some characteristics of researchers, drawn from history and personal experiences around obesity and type 2 diabetes. Some summary messages emerge: •The history of clinical diabetes research has shown how, perhaps through skilful leadership, combining very different personalities, skills and motivations can solve great challenges •Type 2 diabetes is a primary nutritional disease, secondary to the disease-process of obesity, not a primary endocrine disease •Type 2 diabetes is a manifestation of the disease-process of obesity, revealed by weight gain in people with underlying metabolic syndrome genetics/diathesis, mediated in large part at least by reversible ectopic fat accumulation impairing function of organs (liver, pancreas, brown adipose tissue) •Treat overweight/obesity more seriously (defined as a disease-process with multiple organ-specific complications - not as a BMI state or cut-off) •Discuss the complications and risks of T2D openly: remission is as important as for cancers •Offer and support an optimal dietary weight-management programme as soon as possible from diagnosis, specifically aiming for remission oWarn against non-evidence-based programs that look similar or claim to have similar potential: we have fully evidence based programmes oTarget sustained loss of >15kg for Europeans, (possibly less, eg >10kg for Asians?) •Increase future research support to enhance long-term weight loss maintenance. Several approaches need consideration: oPersonalise diet compositions (recognising there is no intrinsic advantage from different carbohydrate/fat content) oNovel diet strategies (eg 5:2, time-restricted, flexible diet compositions) oNew Pharmaceutical agents as adjuncts to diet if necessary oFood supplements to increase endogenous GLP-1 secretion. Read More

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A andomisd, controlled, double blind tudy to assess mechanstic effects of combination therapy of dapagflozin with xenatide QW versus dapagliflozin alone i obese patients with ype 2 diabetes mellitus (RESILIENT): study protocol.

BMJ Open 2021 07 20;11(7):e045663. Epub 2021 Jul 20.

Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.

Introduction: The newer glucose-lowering therapies for type 2 diabetes (T2D), the glucagon-like peptide-1 receptor agonists (GLP1-RAs) and the sodium-glucose co-transporter 2 inhibitors (SGLT2i), have additional clinical benefits beyond improving glycaemic control; promoting weight loss, addressing associated cardiovascular risk factors and reducing macrovascular and microvascular complications. Considering their independent mechanisms of actions, there is a potential for significant synergy with combination therapy, yet limited data exist. This 32-week randomised, double-blind, placebo-controlled trial will gain mechanistic insight into the effects of coadministration of exenatide QW, a weekly subcutaneous GLP1-RA, with dapagliflozin, a once daily oral SGLT2i, on the dynamic, adaptive changes in energy balance, total, regional and organ-specific fat mass and multiorgan insulin sensitivity. Read More

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Effect of beinaglutide treatment on weight loss in Chinese patients with type 2 diabetes mellitus and overweight/obesity.

Arch Endocrinol Metab 2021 Jul 16. Epub 2021 Jul 16.

Shanghai Benemae Pharmaceutical Corporation, Shanghai, China,

Objective: To evaluate the effect of beinaglutide on weight loss and plasma protein patterns of inflammation/obesity relevant cytokines and biomarkers.

Methods: This study involved 36 adult patients with a body mass index (BMI) of ≥ 24 kg/m and T2DM. Beinaglutide was administered for three months. Read More

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Does intervention with GLP-1 receptor agonist semaglutide modulate perception of sweet taste in women with obesity: study protocol of a randomized, single-blinded, placebo-controlled clinical trial.

Trials 2021 Jul 19;22(1):464. Epub 2021 Jul 19.

Department of Endocrinology, Diabetes and Metabolic Diseases, Division of Internal Medicine, University Medical Centre Ljubljana, Zaloška cesta 7, SI-1000, Ljubljana, Slovenia.

Background: Preclinical studies demonstrated that glucagon-like peptide 1 (GLP-1) is locally synthesized in taste bud cells and that GLP-1 receptor exists on the gustatory nerves in close proximity to GLP-1-containing taste bud cells. This local paracrine GLP-1 signalling seems to be specifically involved in the perception of sweets. However, the role of GLP-1 in taste perception remains largely unaddressed in clinical studies. Read More

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Chlorogenic Acid Improves NAFLD by Regulating gut Microbiota and GLP-1.

Front Pharmacol 2021 30;12:693048. Epub 2021 Jun 30.

Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Our previous studies have shown that chlorogenic acid (CGA) could significantly improve acute and chronic liver injury through antioxidant and anti-inflammatory activities. However, its effect on non-alcoholic fatty liver disease (NAFLD) are not entirely clear. This study aims to explore the effect of CGA on NAFLD induced by high-fat diet (HFD) and whether it regulates the gut microbiota and Glucagon-like peptide-1 (GLP-1). 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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Dynamin regulates L cell secretion in human gut.

Mol Cell Endocrinol 2021 Jul 15;535:111398. Epub 2021 Jul 15.

Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA, Australia. Electronic address:

Background: The mechanochemical enzyme dynamin mediates endocytosis and regulates neuroendocrine cell exocytosis. Enteroendocrine L cells co-secrete the anorectic gut hormones glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) postprandially and is a potential therapeutic target for metabolic diseases. In the present study, we aimed to determine if dynamin is implicated in human L cell secretion. Read More

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Sex differences feed into nuclear receptor signaling along the digestive tract.

Biochim Biophys Acta Mol Basis Dis 2021 Jul 14;1867(11):166211. Epub 2021 Jul 14.

Division of Nutritional Sciences, University of Illinois Urbana Champaign, Urbana, IL, United States of America; Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America; Cancer center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America. Electronic address:

Sex differences in physiology are noted in clinical and animal studies. However, mechanisms underlying these observed differences between males and females remain elusive. Nuclear receptors control a wide range of physiological pathways and are expressed in the gastrointestinal tract, including the mouth, stomach, liver and intestine. Read More

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Contemporary Classification of Glucagon-Like Peptide 1 Receptor Agonists (GLP1RAs).

Diabetes Ther 2021 Jul 15. Epub 2021 Jul 15.

Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India.

This communication provides a contemporary classification of glucagon-like peptide 1 receptor agonists (GLP1RAs) based on indication, route, and frequency of administration, which could support a person-centric approach to treatment choice. It includes all recently developed GLP1RAs as well as those in advanced stages of clinical study. Keeping pace with current trends in pharmacology and metabolic medicine, it attempts to bring clarity and simplicity to a complex spread of information. 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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Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes.

Cell Rep 2021 Jul;36(2):109374

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, VIC, Australia; ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, VIC, Australia. Electronic address:

The glucagon-like peptide-1 receptor (GLP-1R) regulates insulin secretion, carbohydrate metabolism, and appetite and is an important target for treatment of type 2 diabetes and obesity. Multiple GLP-1R agonists have entered into clinical trials, with some, such as semaglutide, progressing to approval. Others, including taspoglutide, failed due to the high incidence of side effects or insufficient efficacy. Read More

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Transient antibiotic-induced changes in the neonatal swine intestinal microbiota impact islet expression profiles reducing subsequent function.

Am J Physiol Regul Integr Comp Physiol 2021 Jul 14. Epub 2021 Jul 14.

Department of Agricultural, Food and Nutritional Science, grid.17089.37University of Alberta, Edmonton, Alberta, Canada.

Neonatal antibiotics administered to human infants initiate gut microbiota dysbiosis that may have long-term effects on body weight (BW) and metabolism. We examined antibiotic-induced adaptations in pancreatic islets of the piglet, a well-accepted model of human infant microbiota and pancreas development. Neonatal piglets randomized to amoxicillin (30mg/kg BW/day; n=7, ANTI) or placebo (vehicle control; n=7, CON) from postnatal day (PND)0-13 were euthanized at PND7, 14 and 49. Read More

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The Effects of Glucagon-Like Peptide-1 Receptor Agonists and Dipeptydilpeptidase-4 Inhibitors on Blood Pressure and Cardiovascular Complications in Diabetes.

J Diabetes Res 2021 30;2021:6518221. Epub 2021 Jun 30.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Glucagon-like peptide-1 receptor (GLP-1R) agonists are a class of newly introduced antidiabetic medications that potentially lower blood glucose by several molecular pathways. DPP-4 inhibitors are the other type of novel antidiabetic medications which act by preventing GLP-1 inactivation and thereby increasing the activity levels of GLP-1, leading to more glucose-induced insulin release from islet -cells and suppression of glucagon release. Most patients with diabetes have concurrent hypertension and cardiovascular disorder. Read More

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