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

Verfasser / Beitragende:
[Nigel Irwin, Victor A. Gault, Brian D. Green, Brett Greer, Jane T. McCluskey, Patrick Harriott, Finbarr P.M. O'Harte, Peter R. Flatt]
Ort, Verlag, Jahr:
2004
Enthalten in:
Biological Chemistry, 385/9(2004-09-01), 845-852
Format:
Artikel (online)
ID: 378884034
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024 7 0 |a 10.1515/BC.2004.110  |2 doi 
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245 0 0 |a Effects of short-term chemical ablation of the GIP receptor on insulin secretion, islet morphology and glucose homeostasis in mice  |h [Elektronische Daten]  |c [Nigel Irwin, Victor A. Gault, Brian D. Green, Brett Greer, Jane T. McCluskey, Patrick Harriott, Finbarr P.M. O'Harte, Peter R. Flatt] 
520 3 |a 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. 
540 |a © Walter de Gruyter 
690 7 |a Biochemistry  |2 nationallicence 
690 7 |a Molecular biology  |2 nationallicence 
690 7 |a Cellular biology  |2 nationallicence 
690 7 |a enteroinsular axis  |2 nationallicence 
690 7 |a GIP receptor antagonist  |2 nationallicence 
690 7 |a (Pro3)GIP  |2 nationallicence 
700 1 |a Irwin  |D Nigel  |u Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK  |4 aut 
700 1 |a Gault  |D Victor A.  |u Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK  |4 aut 
700 1 |a Green  |D Brian D.  |u Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK  |4 aut 
700 1 |a Greer  |D Brett  |u Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, UK  |4 aut 
700 1 |a McCluskey  |D Jane T.  |u Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK  |4 aut 
700 1 |a Harriott  |D Patrick  |u Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, UK  |4 aut 
700 1 |a O'Harte  |D Finbarr P.M.  |u Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK  |4 aut 
700 1 |a Flatt  |D Peter R.  |u Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK  |4 aut 
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950 |B NATIONALLICENCE  |P 700  |E 1-  |a Green  |D Brian D.  |u Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Greer  |D Brett  |u Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, UK  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a McCluskey  |D Jane T.  |u Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Harriott  |D Patrick  |u Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, UK  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a O'Harte  |D Finbarr P.M.  |u Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Flatt  |D Peter R.  |u Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Biological Chemistry  |d Walter de Gruyter  |g 385/9(2004-09-01), 845-852  |x 1431-6730  |q 385:9<845  |1 2004  |2 385  |o bchm 
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