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Effects of subchronic treatment with the long-acting glucose-dependent insulinotropic polypeptide receptor agonist, N-AcGIP, on glucose homeostasis in Streptozotocin-induced diabetes

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

Gault, Victor, McClean, Paula, Irwin, Nigel, Power, Gavin J., McCluskey, Janie and Flatt, Peter (2007) Effects of subchronic treatment with the long-acting glucose-dependent insulinotropic polypeptide receptor agonist, N-AcGIP, on glucose homeostasis in Streptozotocin-induced diabetes. PANCREAS, 35 (1). pp. 73-79. [Journal article]

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Abstract

Objectives: N-AcGIP is a potent and dipeptidylpeptidasc IV-resistant analogue of glucose -dependent insulinotropic polypeptide with significantly improved antidiabetic actions in type 2 diabetes. The present study investigated the effects of subchronic treatment with N-AcGIP on glucose homeostasis in a type I model, namely, streptozotocin (STZ)-induced diabetic mice. Methods: Swiss TO mice given a single intraperitoneal injection of STZ (150 mg/kg body weight) received once-daily injection of N-AcGIP (25 nmol/kg body weight) or saline for 20 days and effects on metabolic parameters and islet architecture assessed. Results: Daily injection of N-AcGlP for 20 days did not significantly alter the characteristic STZ-induced changes of pancreatic insulin content, body weight, food intake, glucose, and,glycated hemoglobin levels. Glucose tolerance and insulin sensitivity were also unchanged by N-AcGIP treatment. Circulating insulin was undetectable, and the number of intact islets and insulin expression was greatly reduced in both groups. Some proliferative activity was identified by 5-bromo-2-deoxyuridine staining in the pancreas, but this and expression of glucagon and somatostatin were similar in the 2 groups. Conclusions: These data indicate that subchronic treatment with the Iona-acting glucose-dependent insulinotropic polypeptide receptor agonist, N-AcGIP, does not have beneficial effects in insulin-deficient STZ-diabetic mice. This supports the primary antidiabetic action of this analogue in type 2 diabetes as stimulation of P-cell function and 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
Biomedical Sciences Research Institute > Stratified Medicine
ID Code:2937
Deposited By:Professor Peter Flatt
Deposited On:17 Dec 2009 11:43
Last Modified:15 Oct 2013 16:40

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