Related Experiment Videos
A dietary intervention (high carbohydrate) during the neonatal period causes islet dysfunction in rats
R Aalinkeel1, M Srinivasan, S C Kalhan
1Departments of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York 14214, USA.
Insights
Early high-carbohydrate (HC) milk formula feeding in rat pups causes immediate hyperinsulinemia. This nutritional intervention significantly alters pancreatic function and insulin secretion during the critical suckling period.
Area of Science:
- * Metabolic research
- * Pediatric nutrition
- * Endocrinology
Background:
- * Artificial milk formulas can impact infant development.
- * Early life nutrition influences long-term metabolic health.
- * Hyperinsulinemia in early life is a concern for metabolic disorders.
Purpose of the Study:
- * To investigate the effects of a high-carbohydrate (HC) milk formula on pancreatic function in suckling rats.
- * To evaluate early-onset hyperinsulinemia and its underlying mechanisms.
- * To compare pancreatic function in artificially reared HC pups versus mother-fed (MF) pups.
Main Methods:
- * Artificial rearing of 4-day-old rat pups with a HC milk formula.
- * Pancreatic islet isolation and function studies at 12 days old.
- * Measurement of plasma insulin, glucagon, and islet enzyme activities.
- * Analysis of glucose transporter (GLUT-2) and hexokinase protein levels.
Main Results:
- * HC-fed pups exhibited significantly increased plasma insulin and glucagon levels compared to MF pups.
- * HC islets showed a leftward shift in glucose-stimulated insulin secretion and basal insulin release.
- * Increased activities of key glycolytic and pyruvate metabolism enzymes (glucokinase, hexokinase, GAPDH, PDH complex) were observed in HC islets.
- * Elevated protein expression of GLUT-2 and hexokinase in HC islets.
Conclusions:
- * Early-life nutritional intervention with a HC formula profoundly impacts pancreatic islet function.
- * HC formula feeding during the suckling period leads to hyperinsulinemia.
- * Metabolic adaptations in pancreatic islets suggest a predisposition to altered glucose homeostasis.
Abstract:
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 Ca(2+) 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.