Pharmacological potential of novel agonists for FFAR4 on islet and enteroendocrine cell function and glucose homeostasis.

Pharmacological potential of novel agonists for FFAR4 on islet and enteroendocrine cell function and glucose homeostasis. Eur J Pharm Sci. 2019 Oct 25;:105104 Authors: McCloskey AG, Miskelly MG, Flatt PR, McKillop AM Abstract BACKGROUND: To investigate the metabolic effects of FFAR4-selective agonists on islet and enteroendocrine cell hormone release and the combined therapeutic effectiveness with DPP-IV inhibitors. METHODS: Insulinotropic activity and specificity of FFAR4 agonists were determined in clonal pancreatic BRIN-BD11 cells. Expression of FFAR4 was assessed by qPCR and western blotting following agonist treatment in BRIN-BD11 cells and by immunohistochemistry in mouse islets. Acute in-vivo effects of agonists was investigated after intraperitoneal (i.p.) or oral administration in lean and HFF-obese diabetic mice. RESULTS: GSK137647 (10-11-10-4 M) and Compound-A (10-10-10-4 M) stimulated insulin secretion at 5.6mM (p
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research

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ConclusionsRepeated administration of DR1060 provides potent and sustained glycemic control and body weight loss effect in high-fat DIO mice. DR10601 is a promising long-acting agent deserving further investigation for the treatment of type 2 diabetes and obesity.
Source: Journal of Endocrinological Investigation - Category: Endocrinology Source Type: research
Publication date: Available online 20 November 2019Source: PeptidesAuthor(s): Sravan K. Thondam, Daniel J. Cuthbertson, John P.H. WildingAbstractGlucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide (GLP-1) are the two incretin hormones secreted by the enteroendocrine system in response to nutrient ingestion. Compared with GLP-1, GIP is less well studied as a hormone or as a potential pharmacological treatment. Beyond its insulinotropic effects in the pancreas, GIP has important biological actions in many other tissues but its role in dietary fat metabolism and lipid storage in adipose tissue has bee...
Source: Peptides - Category: Biochemistry Source Type: research
Publication date: Available online 19 November 2019Source: PeptidesAuthor(s): Clifford J. BaileyAbstractThe potential application of glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide, GIP) in the management of obesity and type 2 diabetes has been controversial. Initial interest in the therapeutic use of GIP was dampened by evidence that its insulinotropic activity was reduced in type 2 diabetes and by reports that it increased glucagon secretion and adipose deposition in non-diabetic individuals. Also, attention was diverted away from GIP by the successful development of glucagon-like peptide-1 (...
Source: Peptides - Category: Biochemistry Source Type: research
Obesity and related metabolic disorders, including type 2 diabetes mellitus (T2DM), alarmingly grow up in the modern society thus representing a serious issue for endocrinology and medicine. Obesity is the major risk factor for T2DM [1], however, not all obese individuals ultimately develop T2DM. Nevertheless, mechanisms linking obesity to T2DM are being extensively studied.
Source: Diabetes Research and Clinical Practice - Category: Endocrinology Authors: Source Type: research
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
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Source: Journal of Diabetes Investigation - Category: Endocrinology Authors: Tags: Updates 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
Abstract T1R3 protein, the main subunit of the sweet taste receptor and receptor of amino acid taste, is expressed in the epithelium of the tongue and gastrointestinal tract, in β cells of the pancreas, hypothalamus, and numerous other organs. Recently, convincing evidences on the involvement of T1R3 in the control of carbohydrate and lipid metabolism, and the control of incretin and insulin production were obtained. In the study on Tas1r3-gene knockout mouse strain and parent C57BL/6J strain as a control, the data on the effect of T1R3 on morphological characteristics of Langerhans islets in the pancreas wer...
Source: Doklady Biological Sciences - Category: Biology Authors: Tags: Dokl Biol Sci Source Type: research
From the Incretin Concept and the Discovery of GLP-1 to Today's Diabetes Therapy Jens Juul Holst* Department of Biomedical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Researchers have been looking for insulin-stimulating factors for more than 100 years, and in the 1960ties it was definitively proven that the gastrointestinal tract releases important insulinotropic factors upon oral glucose intake, so-called incretin hormones. The first significant factor identified was the duodenal glucose-dependent insulinotropic polypeptide, GIP, wh...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Alyce M. Martin1, Emily W. Sun1, Geraint B. Rogers2,3 and Damien J. Keating1,4* 1Molecular and Cellular Physiology Laboratory, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia 2Microbiome Research Laboratory, Flinders University, Adelaide, SA, Australia 3Infection and Immunity, South Australian Health and Medical Research Institute, Adelaide, SA, Australia 4Nutrition and Metabolism, South Australian Health and Medical Research Institute, Adelaide, SA, Australia The microbial community of the gut conveys significant benefits to host physiology. A clear relationship has now bee...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
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