caa a22 4500 378884034 CHVBK 20180305123438.0 cr unu---uuuuu 161128e20040901xx s 000 0 eng 10.1515/BC.2004.110 doi (NATIONALLICENCE)gruyter-10.1515/BC.2004.110 Effects of short-term chemical ablation of the GIP receptor on insulin secretion, islet morphology and glucose homeostasis in mice [Elektronische Daten] [Nigel Irwin, Victor A. Gault, Brian D. Green, Brett Greer, Jane T. McCluskey, Patrick Harriott, Finbarr P.M. O'Harte, Peter R. Flatt] Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by endocrine K-cells in response to nutrient absorption. In this study we have utilized a specific and enzymatically stable GIP receptor antagonist, (Pro3)GIP, to evaluate the contribution of endogenous GIP to insulin secretion and glucose homeostasis in mice. Daily injection of (Pro3)GIP (25 nmol/kg body weight) for 11 days had no effect on food intake or body weight. Non-fasting 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 (Pro3)GIP treated mice compared to control (p<0.01). Glucose-mediated insulin secretion was not significantly different between the two groups. Insulin sensitivity of 11-day (Pro3)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 (Pro3)GIP treated mice and controls. However, (Pro3)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 (Pro3)GIP treated mice. The observed biological effects of (Pro3)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. © Walter de Gruyter Biochemistry nationallicence Molecular biology nationallicence Cellular biology nationallicence enteroinsular axis nationallicence GIP receptor antagonist nationallicence (Pro3)GIP nationallicence Irwin Nigel Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK aut Gault Victor A. Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK aut Green Brian D. Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK aut Greer Brett Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, UK aut McCluskey Jane T. Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK aut Harriott Patrick Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, UK aut O'Harte Finbarr P.M. Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK aut Flatt Peter R. Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK aut Biological Chemistry Walter de Gruyter 385/9(2004-09-01), 845-852 1431-6730 385:9<845 2004 385 bchm https://doi.org/10.1515/BC.2004.110 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/BC.2004.110 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Irwin Nigel Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK aut NATIONALLICENCE 700 1- Gault Victor A. Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK aut NATIONALLICENCE 700 1- Green Brian D. Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK aut NATIONALLICENCE 700 1- Greer Brett Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, UK aut NATIONALLICENCE 700 1- McCluskey Jane T. Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK aut NATIONALLICENCE 700 1- Harriott Patrick Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, UK aut NATIONALLICENCE 700 1- O'Harte Finbarr P.M. Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK aut NATIONALLICENCE 700 1- Flatt Peter R. Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK aut NATIONALLICENCE 773 0- Biological Chemistry Walter de Gruyter 385/9(2004-09-01), 845-852 1431-6730 385:9<845 2004 385 bchm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter