Peptides come to the rescue of pancreatic {beta} cells Cell Biology

IntroductionInsulin and glucagon are well-known peptide hormones that keep glucose levels within a healthy range in the body. But they are only part of a complex network that controls concentrations of this ubiquitous sugar in blood and tissues. Other molecules regulate glucose by controlling insulin secretion from the pancreas or protecting pancreatic β cells against stresses that lead to cellular dysfunction or cell death (1).One of these protective regulators is glucagon-like peptide 1 (GLP-1), a 30-amino-acid-long peptide produced in specialized epithelial cells of the intestine, called L cells, and also in the brain and other organs and tissues (2).GLP-1 belongs to a group of peptides that mediate the “incretin effect,” an endocrine response to glucose arising from food digestion in the intestines (2, 3). This response helps regulate food intake and the fate of dietary glucose. Specifically, GLP-1 is released from the intestinal cells when food is ingested and then binds to and activates the GLP-1 receptor (GLP-1R), a G protein–coupled receptor on many cell types, including β cells in which GLP-1R signaling stimulates insulin synthesis and secretion (3). Notably, the incretin effect stimulates insulin secretion from pancreatic β cells more strongly than exposure to glucose alone.An article published in the Journal of Biological Chemistry (4), recognized as a Classic here, added to our understanding of the incretin effect by showing that G...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Classics Source Type: research

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ConclusionsSince its discovery, GLP-1 has emerged as a pleiotropic hormone with a myriad of metabolic functions that go well beyond its classical identification as an incretin hormone. The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders
Source: Molecular Metabolism - Category: Endocrinology Source Type: research
In this study we evaluated if the intake of an oleuropein-enriched chocolate could have positive effects on glycaemia and insulin levels in patients with type 2 diabetes mellitus (T2DM) and healthy subjects (HS).
Source: Clinical Nutrition - Category: Nutrition Authors: Tags: Original article Source Type: research
Evidence about the treatment of hospitalized type  2 diabetes patients with incretin‐based therapy has emerged in the past 15 years. Based on this evidence, dipeptidyl peptidase‐4 inhibitors should be considered for hospitalized patients with type 2 diabetes and an algorithm for this is proposed. In relation to use of glucagon‐like peptide ‐1 and glucagon‐like peptide‐1 receptor agonist, further research is required to help define their role in the inpatient setting.
Source: Journal of Diabetes Investigation - Category: Endocrinology Authors: Tags: Letter to the Editor Source Type: research
Abstract CONTEXT: It is not known whether GLP-1 and GIP levels correlate within individuals, nor whether levels change with age. Previous studies have all been cross-sectional in design. OBJECTIVE: To evaluate longitudinal changes in fasting and glucose-stimulated incretin hormone concentrations in healthy older subjects. PATIENTS AND DESIGN: 41 healthy older subjects had measurements of plasma GLP-1 and GIP while fasting and after a 75g oral glucose load on two occasions separated by 5.9 ± 0.1 years (mean age at the initial study was 71.2 ± 3.8 (SD) years). Breath samples were collected to...
Source: The Journal of Clinical Endocrinology and Metabolism - Category: Endocrinology Authors: Tags: J Clin Endocrinol Metab Source Type: research
In this study, the predicted compounds were suggested as potent anti-diabetic candidates. Chosen structures were applied following computational strategies: The generation of the three-dimensional quantitative structure-activity relationship (3D QSAR) pharmacophore models, virtual screening, molecular docking, and de novo Evolution. The method also validated by performing re-docking and cross-docking studies of seven protein systems for which crystal structures were available for all bound ligands. The molecular docking experiments of predicted compounds within the binding pocket of DPP-IV were conducted. By using 25 train...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
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Source: Journal of Diabetes Investigation - Category: Endocrinology Authors: Tags: Updates Source Type: research
Publication date: Available online 23 July 2019Source: Nutrition, Metabolism and Cardiovascular DiseasesAuthor(s): Barchetta I, Ciccarelli G, Barone E, Cimini FA, Ceccarelli V, Bertoccini L, Sentinelli F, Tramutola A, Del Ben M, Angelico F, Baroni MG, Lenzi A, Cavallo MGAbstractBackgroundDipeptidyl peptidase 4 (DPP4) is a key enzyme involved in the regulation of the incretin system exerted by cleaving the glucagon-like peptide 1 (GLP-1); the blockage of DPP4, exerted by the antidiabetic agents DPP4-inhibitors (DPP4-I), results in greater GLP-1 concentration and improved glycaemic control. DPP4 acts also as a pro-inflammato...
Source: Nutrition, Metabolism and Cardiovascular Diseases - Category: Nutrition Source Type: research
In this study, we further examined its abilities in regulating blood glucose in diabetic mice. We found that supaglutide stimulated insulin secretion in both mouse and human islets in a dose-dependent fashion. Oral glucose tolerance test conducted in normal ICR mice showed that supaglutide significantly decreased postprandial glucose excursions in a dose-dependent fashion. In type 2 diabetic db/db mice, a single-dose injection of supaglutide significantly decreased blood glucose levels, and this efficacy was lasted for at least 72 h in a dose-dependent fashion. During a 4-week intervention course supaglutide (twice injecti...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Dipeptidyl peptidase 4 (DPP4) is a key enzyme involved in the regulation of the incretin system exerted by cleaving the glucagon-like peptide 1 (GLP-1); the blockage of DPP4, exerted by the antidiabetic agents DPP4-inhibitors (DPP4-I), results in greater GLP-1 concentration and improved glycaemic control. DPP4 acts also as a pro-inflammatory molecule and mediates vascular damage in experimental models. The relationship between DPP4 activity and endothelial function in diabetes has not been explored yet.
Source: Nutrition, Metabolism, and Cardiovascular Diseases : NMCD - Category: Nutrition Authors: Source Type: research
Hypoglycaemia is common in both type 1 and type 2 diabetes and has both acute and long-term consequences. Therefore, a key to proper glucose-lowering therapy in diabetes is to avoid or prevent hypoglycaemia. Incretin therapy (DPP-4 inhibitors and GLP-1 receptor agonists) offers an advantage in this respect, because it reduces glucose with a low risk of hypoglycaemia, both in monotherapy and in combination with other therapies. The reason for this low risk of hypoglycaemia is the glucose dependency of action of incretin therapy and the sustainment of glucose counter-regulatory hormone responses to hypoglycaemia, in particul...
Source: Metabolism - Clinical and Experimental - Category: Biomedical Science Authors: Source Type: research
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