No evidence of tachyphylaxis for insulinotropic actions of Glucose-Dependent Insulinotropic Polypeptide (GIP) in subjects with type 2 diabetes, their first-degree relatives, or in healthy subjects

Publication date: Available online 25 October 2019Source: PeptidesAuthor(s): M.A. Nauck, H. Holle, M. Kahle, A. Tytko, C.F. Deacon, J.J. Holst, J.J. MeierAbstractBackground, aimsIn patients with type 2 diabetes, the lost insulinotropic effect of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) is more apparent after continuous versus bolus administration. To test whether the difference might be explained by rapid tachyphylaxis in response to elevated concentrations of GIP, and whether patients with type 2 diabetes and their relatives are more susceptible to tachyphylaxis than healthy subjects.Patients and MethodsIn a two-way crossover design, insulinotropic responses to repeated bolus injection (50 pmol/kg body weight at 30 and 120 min) and continuous infusion of GIP (2 pmol.kg-1.min-1 from 30-180 min) under hyperglycaemic clamp conditions (8.5 mmol/l) was compared in age- gender- and weight-matched patients with type 2 diabetes, first degree relatives of such patients, and healthy subjects.ResultsInsulin secretory responses to the first and second GIP bolus were not significantly different in any of the subject groups. Subjects with type 2 diabetes had a significant relative impairment versus healthy subjects with continuous (C-peptide, -13.2 %, p 
Source: Peptides - Category: Biochemistry Source Type: research

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Publication date: Available online 12 December 2019Source: PeptidesAuthor(s): Jens Juul Holst, Mette Marie RosenkildeAbstractRecently GIP-GLP-1 co-agonists with powerful effects on glycemic control and body weight in patients with type 2 diabetes have been described. While such effects are the expected ones from a glucagonlike peptide-1 receptor agonist, similar contributions from the GIP component of the co-agonist would be surprising and contrast to the existing literature. Conventionally, GIP is thought of as an important incretin hormone regulating postprandial insulin secretion in glucose tolerant individuals, but suc...
Source: Peptides - Category: Biochemistry Source Type: research
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
Purpose of review Incretin-based therapies mimic or augment the gut-hormone glucagon-like peptide (GLP)-1 and, due to their glucose-lowering potential and beneficial safety profile, as well as their cardiovascular safety and/or protection, are prescribed on a large scale to treat individuals with type 2 diabetes (T2D). However, whether the two drug-classes that belong to this category, respectively GLP-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors, also reduce the risk of diabetic kidney disease (DKD) is at present heavily debated. This review aims to discuss the current evidence. Recent findings Evi...
Source: Current Opinion in Nephrology and Hypertension - Category: Urology & Nephrology Tags: HORMONES, AUTACOIDS, NEUROTRANSMITTERS AND GROWTH FACTORS: Edited by Mark Cooper and Merlin Thomas 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
Publication date: Available online 7 November 2019Source: PeptidesAuthor(s): Carolyn F DeaconAbstractGlucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone with insulinotropic and glucagonotropic actions, and is believed to be the more physiologically important incretin hormone in healthy humans. Together with the other incretin hormone, glucagon-like peptide-1 (GLP-1), it plays an important role in regulating glucose homeostasis. Both GLP-1 and GIP are substrates of the enzyme dipeptidyl peptidase-4 (DPP-4), and DPP-4 inhibitors, which potentiate their effects on glycaemic control, are now used t...
Source: Peptides - Category: Biochemistry Source Type: research
ConclusionsOur findings suggest that, in an unselected population, the use of both classes of incretin-based medications is not associated with an increased risk of cholangiocarcinoma.
Source: Acta Diabetologica - Category: Endocrinology Source Type: research
Publication date: Available online 3 November 2019Source: PeptidesAuthor(s): Lærke S. Gasbjerg, Natasha C. Bergmann, Signe Stensen, Mikkel B. Christensen, Mette M. Rosenkilde, Jens J. Holst, Michael Nauck, Filip K. KnopAbstractGlucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) potentiate glucose-induced insulin secretion and are therefore thought to be responsible for the incretin effect. The magnitude of the incretin effect, defined as the fraction of postprandial insulin secretion stimulated by intestinal factors, has been reported to be up to ∼60% in healthy individuals. In ...
Source: Peptides - Category: Biochemistry Source Type: research
Abstract Macrophages play a critical role in the immune response against pathogen invasion and injury. However, under pathological stress, macrophages could have aberrant roles and contribute to the pathogenesis of inflammatory associated diseases. Exenatide is a glucagon-like peptide 1(GLP-1) agonist, which belongs to the family of synthetic exendin-based incretin mimetic. Exendin related compounds reduce glucose levels in type 2 diabetes patients. The purpose of this study was to examine the anti-inflammatory effects of exendin-4 in LPS-induced activation of macrophages. We show that exendin-4 inhibits LPS-induc...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
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