Glucose-dependent insulinotropic polypeptide (GIP) is released from the upper small intestine in response to food intake and contributes to the postprandial control of nutrient disposition, including of sugars and fats. Long neglected as a potential therapeutic target, the GIPR axis has received increasing interest recently, with the emerging data demonstrating the metabolically favorable outcomes of adding GIPR agonism to GLP-1 receptor agonists in people with type 2 diabetes and obesity. This review examines the physiology of the GIP axis, from the mechanisms underlying GIP secretion from the intestine to its action on target tissues and therapeutic development.
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| http://dx.doi.org/10.1146/annurev-nutr-062320-113625 | DOI Listing |
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A novel bombesin-related peptide modulates glucose tolerance and insulin secretion in non-obese and hypothalamic-obese rats.
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Universidade Estadual do Oeste do Paraná, Programa de Pós-Graduação em Biociências e Saúde (PPG-BCS), Cascavel, Brazil.
This study investigated the effects of a novel bombesin-related peptide (BR-b), derived from the skin of the Chaco tree frog (Boana raniceps), on glucose homeostasis in non-obese and hypothalamic-obese male rats. Hypothalamic obesity was induced in neonatal rats through high-dose administration of monosodium glutamate (MSG; 4 g/kg), while control animals (CTL) received an equimolar saline solution. At 70 days of age, both MSG and CTL groups underwent an oral glucose tolerance test (OGTT; 2 g/kg) with or without prior intraperitoneal administration of BR-b at doses of 0.
View Article and Find Full Text PDFChronic GIPR agonism results in pancreatic islet GIPR functional desensitisation.
Mol Metab
January 2025
Section of Endocrinology and Investigative Medicine, Imperial College London, United Kingdom. Electronic address:
Objectives: There is renewed interest in targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) for treatment of obesity and type 2 diabetes. G-protein coupled receptor desensitisation is suggested to reduce the long-term efficacy of glucagon-like-peptide 1 receptor (GLP-1R) agonists and may similarly affect the efficacy of GIPR agonists. We explored the extent of pancreatic GIPR functional desensitisation with sustained agonist exposure.
View Article and Find Full Text PDFDose-related effects of calcium to enhance the effects of L-tryptophan on gut hormones and energy intake in obesity.
J Clin Endocrinol Metab
January 2025
Adelaide Medical School, University of Adelaide, Adelaide, Australia.
Context: In males of normal weight, intraduodenal administration of calcium enhances the effects of the amino acid, L-tryptophan (Trp), to suppress energy intake, associated with greater stimulation of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY) secretion (key mechanisms underlying the regulation of pyloric motility and gastric emptying), but not gastrin or glucose-dependent insulinotropic polypeptide (GIP).
Objective: Given the implications for the management of obesity, the current study evaluated the effects of calcium, when administered alone and in combination with Trp, on gut hormone secretion, antropyloroduodenal motility and energy intake in males with obesity.
Methods: Fifteen males with obesity and without type 2 diabetes (mean±SD; age: 27±8 years; body mass index: 30±2 kg/m2; HbA1c: 5.
Elective peri-operative management of adults taking glucagon-like peptide-1 receptor agonists, glucose-dependent insulinotropic peptide agonists and sodium-glucose cotransporter-2 inhibitors: a multidisciplinary consensus statement: A consensus statement from the Association of Anaesthetists, Association of British Clinical Diabetologists, British Obesity and Metabolic Surgery Society, Centre for Perioperative Care, Joint British Diabetes Societies for Inpatient Care, Royal College of Anaesthetists, Society for Obesity and Bariatric Anaesthesia and UK Clinical Pharmacy Association.
Anaesthesia
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Department of Medicine, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK.
Introduction: Glucagon-like peptide-1 receptor agonists, dual glucose-dependent insulinotropic peptide receptor agonists and sodium-glucose cotransporter-2 inhibitors are used increasingly in patients receiving peri-operative care. These drugs may be associated with risks of peri-operative pulmonary aspiration or euglycaemic ketoacidosis. We produced a consensus statement for the peri-operative management of adults taking these drugs.
View Article and Find Full Text PDFThe other side of the incretin story: GIPR signaling in energy homeostasis.
Cell Metab
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Departments of Cellular & Molecular Physiology and Internal Medicine (Endocrinology), Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address:
Incretin receptor agonists have been effective in combatting obesity and diabetes. While the body of knowledge regarding the signaling mechanisms of glucagon-like peptide 1 (GLP-1) receptor agonists is ever-growing, glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists are less understood. The previewed papers offer insight into the impact of adipose GIPR on energy and weight homeostasis.
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