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Am J Physiol Endocrinol Metab 292: E1069-E1078, 2007. First published December 12, 2006; doi:10.1152/ajpendo.00477.2006
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Role of the autonomic nervous system in the development of hyperinsulinemia by high-carbohydrate formula feeding to neonatal rats

Department of Biochemistry, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York

Submitted 7 September 2006 ; accepted in final form 5 December 2006

An early dietary intervention in the form of a high-carbohydrate (HC) milk formula in neonatal rat pups results in immediate onset of hyperinsulinemia. While increased insulin secretion in HC rats has been shown to be related to hypersensitivity to glucose, the immediate onset of hyperinsulinemia and its persistence throughout the suckling period suggest involvement of multiple systems that enhance insulin secretion in response to increased demand. Evidence presented here in 12-day-old HC rats indicates that altered activity of the autonomic nervous system contributes to enhanced insulin secretory responses to glucose stimulation through increased parasympathetic and decreased sympathetic signaling. Both in vivo and in vitro studies have shown that HC rats secrete significantly higher levels of insulin in response to glucose in the presence of acetylcholine, a cholinergic agonist, while sensitivity to inhibition of insulin secretion by oxymetazoline, an _2a-adrenergic receptor (_2aAR) agonist, was reduced. In addition, HC rats showed increased sensitivity to blockade of cholinergic-induced insulin secretion by the muscarinic type 3 receptor (M3R) antagonist 4-diphenylacetoxy-N-methylpiperidine methobromide, as well as increased potentiation of glucose-stimulated insulin secretion by treatment with yohimbine. Increases in islets levels of M3R, phospholipase C-1, and protein kinase C mRNAs, as well as decreased _2aAR mRNA, in 12-day-old HC rats provide a mechanistic connection to the changes in insulin secretion seen in HC rats. In conclusion, altered autonomic regulation of insulin secretion, due to the HC nutritional intervention, contributes to the development of hyperinsulinemia in 12-day-old HC rats.

high-carbohydrate milk formula; parasympathetic nervous system; sympathetic nervous system

This article has been cited by other articles:

				P. Mitrani, M. Srinivasan, C. Dodds, and M. S. Patel Autonomic involvement in the permanent metabolic programming of hyperinsulinemia in the high-carbohydrate rat model Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1364 - E1377. [Abstract] [Full Text] [PDF]