Impaired insulin secretion in perfused pancreases isolated from offspring of female rats fed a low protein whey-based diet

Context: Insufficient maternal protein intake as been postulated to cause impaired fuel metabolism and diabetes mellitus, in adult mammalian progeny, but the mechanism remains unclear. Objective: To investigate the effect of a matZmal low protein whey-based diet during pregnancy and lactation on pancreatic function and skeletal muscle glucose metabolism in the offspring. Animals: Sprague-Dawley rats: 8 mothers and 46 offspring. Design: Female rats were fed throughout pregnancy and lactation with otherwise-complete isoenergetic diets sufficient (20% whey protein; control: n=3) or insufficient (5% whey protein; low-protein: n=5) in whey protein. From weaning all offspring ate control diet. Main outcome measures: Food intake and weight gain were measured for both mothers and offspring, and in vitro functional studies of endocrine pancreas and skeletal muscle were performed on offspring at 40 and 50 days of age, respectively. Results: Food intake (P=0.004) and weight gain (P=0.006) were lower in low protein than control mothers during early gestation. Offspring of low protein mothers had significant lower body weight from 5 to 15 days of age, although there was no significant difference in food consumption. Glucose, arginine- and glucose/arginine-stimulated insulin secretion from perfused pancreases isolated from low protein offspring were decreased by between 55 and 65% compared with control values. Studies in skeletal muscle demonstrated no difference in insulin sensitivity between the two groups. Conclusions: Dietary whey protein insufficiency in female rats during pregnancy and lactation can evoke major changes in insulin secretion in progeny, and these changes represent a persistent functional abnormality in the endocrine pancreas.