Effects of Subchronic Treatment With the Long-Acting Glucose-Dependent Insulinotropic Polypeptide Receptor Agonist, N-AcGIP, on Glucose Homeostasis in Streptozotocin-Induced Diabetes
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Date
2007-07-01
Authors
Gault, Victor A.
McClean, Paula L.
Irwin, Nigel
Power, Gavin J.
McCluskey, Jane T.
Flatt, Peter R.
Citation
Gault, V.A., McClean, P.L., Irwin, N., Power, G.J., McCluskey, J.T. and Flatt, P.R. (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. Available at: https://doi.org/10.1097/mpa.0b013e31804fa19a.
Abstract
OBJECTIVES:
N-AcGIP is a potent and dipeptidylpeptidase 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 1 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-AcGIP 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 long-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 beta-cell function and insulin secretion.