The glucose-dependent insulinotropic polypeptide signaling axis in the central nervous system

Publication date: Available online 4 November 2019Source: PeptidesAuthor(s): A.E. Adriaenssens, F.M. Gribble, F. ReimannAbstractGlucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone released from the epithelium of the upper small intestine. While GIP shares common actions on the pancreatic beta cell with glucagon-like peptide-1 (GLP-1), unlike GLP-1, GIP presents a complex target for the development of diabetes and obesity therapies due to its extra-pancreatic effects on fat mass. Recent pharmacological developments, however, have provided insight into a previously unrecognized role for GIP receptor (GIPR) signaling in regulating appetite. Additionally, GIP-based therapeutics have demonstrated promising neuroprotective properties. Together these observations identify an important central component of the GIP/GIPR signaling axis, and have triggered a resurgence of research interest into the central actions of GIP. In this review, we discuss what is currently known about where GIP may act in the central nervous system (CNS), the characteristics of its target cell populations, and the physiological effects of manipulating the activity Gipr-expressing cells in the brain.
Source: Peptides - Category: Biochemistry 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
Publication date: Available online 18 November 2019Source: PeptidesAuthor(s): Rabeet Khan, Alejandra Tomas, Guy A. RutterAbstractGlucose-dependent insulinotropic polypeptide (GIP) is a gut-derived incretin that, in common with glucagon-like peptide-1 (GLP-1), has both insulin releasing and extra-pancreatic glucoregulatory actions. GIP is released in response to glucose or fat absorption and acts on the GIP receptor (GIPR) to potentiate insulin release from pancreatic beta cells. GIP has also been shown to promote beta cell survival and stimulate the release of GLP-1 from islet alpha cells. There is now evidence to suggest ...
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
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...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci 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
CONCLUSION: The present study does not provide evidence to support that dietary supplementation with the NAD+ precursor NR serves to impact glucose tolerance, β-cell secretory capacity, α-cell function, and incretin hormone secretion in obese, non-diabetic males. Moreover, bile acid levels in plasma did not change in response to NR supplementation. PMID: 31390002 [PubMed - as supplied by publisher]
Source: The Journal of Clinical Endocrinology and Metabolism - Category: Endocrinology Authors: Tags: J Clin Endocrinol Metab 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
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