Ulster University Logo

Ulster Institutional Repository

Effects of short-term chemical ablation of the GIP receptor on insulin secretion, islet morphology and glucose homeostasis in mice

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Irwin, Nigel, Gault, Victor, Green, BD, Greer, B, McCluskey, Janie, Harriott, P, O'Harte, Finbarr and Flatt, Peter (2004) Effects of short-term chemical ablation of the GIP receptor on insulin secretion, islet morphology and glucose homeostasis in mice. BIOLOGICAL CHEMISTRY, 385 (9). pp. 845-852. [Journal article]

Full text not available from this repository.

DOI: 10.1515/BC.2004.110

Abstract

Glucose dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by endocrine Kcells in response to nutrient absorption. In this study we have utilized a specific and enzymatically stable GIP receptor antagonist, (Pro(3))GIP, to evaluate the contribution of endogenous GIP to insulin secretion and glucose homeostasis in mice. Daily injection of (Pro(3))GIP (25 nmol/kg body weight) for 11 days had no effect on food intake or body weight. Nonfasting plasma glucose concentrations were significantly raised (p<0.05) by day 11, while plasma insulin concentrations were not significantly different from saline treated controls. After 11 days, intraperitoneal glucose tolerance was significantly impaired in the (Pro(3))GIP treated mice compared to control (p<0.01). Glucosemediated insulin secretion was not significantly different between the two groups. Insulin sensitivity of 11-day (Pro(3))GIP treated mice was slightly impaired 60 min post injection compared with controls. Following a 15 min refeeding period in 18 h fasted mice, food intake was not significantly different in (Pro(3))GIP treated mice and controls. However, (Pro(3))GIP treated mice displayed significantly elevated plasma glucose levels 30 and 60 min post feeding (p<0.05, in both cases). Postprandial insulin secretion was not significantly different and no changes in pancreatic insulin content or islet morphology were observed in (Pro(3))GIP treated mice. The observed biological effects of (Pro(3))GIP were reversed following cessation of treatment for 9 days. These data indicate that ablation of GIP signaling causes a readily reversible glucose intolerance without appreciable change of insulin secretion.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:3016
Deposited By:Professor Peter Flatt
Deposited On:13 Jan 2010 16:06
Last Modified:19 Nov 2012 16:27

Repository Staff Only: item control page