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Am J Physiol Endocrinol Metab 277: E1061-E1069, 1999;
0193-1849/99 $5.00
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Vol. 277, Issue 6, E1061-E1069, December 1999

A dietary intervention (high carbohydrate) during the neonatal period causes islet dysfunction in rats

Ravikumar Aalinkeel1, Malathi Srinivasan1, Satish C. Kalhan2, Suzanne G. Laychock3, and Mulchand S. Patel1

1 Departments of Biochemistry and 3 Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York 14214; and 2 Center for Metabolism and Nutrition, Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio 44109

Artificial rearing of 4-day-old rat pups on a high-carbohydrate (HC) milk formula results in the immediate onset of hyperinsulinemia. To evaluate these early changes, studies on pancreatic function were carried out on 12-day-old HC rats and compared with age-matched mother-fed (MF) pups. The plasma insulin and glucagon contents were increased sixfold and twofold, respectively, in HC rats compared with MF rats. There was a distinct leftward shift in the glucose-stimulated insulin secretory pattern for HC islets. HC islets secreted insulin in the absence of any added glucose and in the presence of Ca2+ channel inhibitors. The activities of glucokinase, hexokinase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate dehydrogenase complex were significantly increased in HC islets compared with MF islets. The protein contents of GLUT-2 and hexokinase were significantly increased in HC islets. These findings indicate that a nutritional intervention in the form of a HC formula only during the suckling period has a profound influence on pancreatic function, causing the onset of hyperinsulinemia.

newborn rats; nutritional modification; insulin secretion; beta -cell metabolism


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