The early history of GIP 1969-2000: from enterogastrone to major metabolic hormone

Publication date: Available online 17 September 2019Source: PeptidesAuthor(s): Vincent MarksAbstractThis paper describes the early history of Gastric Inhibitory Polypeptide, better referred to simply as GIP, from its isolation by purification from a crude preparation of CCK-PZ (cholecystokinin/pancreozymin) to its recognition as a key play in the pathogenesis of obesity and other metabolic disorders far removed from the enterogastrone properties by which it was originally identified. Augmentation of glucose mediated insulin release, the incretin effect, was discovered soon after GIP was first isolated and only much later was its important role in the pathogenesis of obesity, through mechanism other than its insulin secretion, appreciated. Immunoassay – the method by which the concentration of GIP was measured in plasma until quite recently – was found to be flawed and to depend upon which specific epitope of the hormone an assay detected. This was especially true if it was an amino-acid sequence specific to porcine rather than human GIP. A further confounder was the discovery that much of the GIP measured by immunoassay was its biological antagonist produced by cleavage of its two N-terminal amino-acids in the circulation by the same dipeptidyl-peptidase as de-activates GLP-1. Potential use of synthetic agonistic and antagonistic GIP analogues in therapeutics was barely alluded to before year 2000.
Source: Peptides - Category: Biochemistry Source Type: research

Related Links:

Publication date: December 2019Source: Peptides, Volume 122Author(s): Vincent MarksAbstractThis paper describes the early history of Gastric Inhibitory Polypeptide, better referred to simply as GIP, from its isolation by purification from a crude preparation of CCK-PZ (cholecystokinin/pancreozymin) to its recognition as a key player in the pathogenesis of obesity and other metabolic disorders far removed from the enterogastrone properties by which it was originally identified. Augmentation of glucose mediated insulin release, the incretin effect, was discovered soon after GIP was first isolated and only much later was its ...
Source: Peptides - Category: Biochemistry 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
ConclusionsOur data demonstrate an interaction between a peripheral hormonal signal and central nervous activity as robust predictor of body weight change throughout the different periods of a long-term life-style intervention. The preeminent role of their interdependency compared to the partly ambivalent effects of the single components argues for integrative approaches to improve sensitivity and reliability of weight prediction conventionally based on individual biomarkers.
Source: Molecular Metabolism - Category: Endocrinology Source Type: research
Nutrient excess, a major driver of obesity, diminishes hypothalamic responses to exogenously administered leptin, a critical hormone of energy balance. Here, we aimed to identify a physiological signal that arises from excess caloric intake and negatively controls hypothalamic leptin action. We found that deficiency of the gastric inhibitory polypeptide receptor (Gipr) for the gut-derived incretin hormone GIP protected against diet-induced neural leptin resistance. Furthermore, a centrally administered antibody that neutralizes GIPR had remarkable antiobesity effects in diet-induced obese mice, including reduced body weigh...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: 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
ConclusionAn increase in GLP-1 response was not preserved at 4  years, but a significant increase in GIP response was observed along with improved glycaemic control following LSG.
Source: Obesity Surgery - Category: Surgery Source Type: research
This article is protected by copyright. All rights reserved.
Source: Journal of Diabetes Investigation - Category: Endocrinology Authors: Tags: Updates Source Type: research
Abstract Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates postprandial glycaemic response by enhancing insulin secretion. We previously demonstrated that the postprandial GLP-1 response was enhanced during the development of diet-induced obesity in rats. However, the physiological relevance of the enhanced GLP-1 response remained unclear. We aimed to determine the role of endogenous GLP-1 during obesity development. Male Sprague-Dawley rats were given either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose, weight basis) diet with or without continuous administration o...
Source: The British Journal of Nutrition - Category: Nutrition Authors: Tags: Br J Nutr 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
Incretins have risen to the forefront of therapies for obesity and related metabolic complications, primarily because of their efficacy and relatively few side effects. Importantly, their efficacy in altering energy balance and decreasing body weight is apparently through actions in the central nervous system (CNS); the latter may have implications beyond obesity per se, i.e. in other disease states associated with obesity including CNS-related disorders. Here, we first describe the role of the CNS in energy homeostasis and then the current state of knowledge in terms of incretins ’ physiology, pathophysiology and ef...
Source: Metabolism - Clinical and Experimental - Category: Biomedical Science Authors: Source Type: research
More News: Biochemistry | Eating Disorders & Weight Management | Gastroenterology | Hormones | Incretin Therapy | Insulin | Obesity