Impaired pancreatic function contributes to the age‐dependent development of metabolic syndrome in female intrauterine growth restricted rats.

Abstract

Birth weight is inversely related to impaired metabolic health. The female intrauterine growth restricted (IUGR) rat exhibits an age‐dependent increase in blood pressure associated with a marked increase in body fat and leptin. Whether increased adiposity is associated with glucose intolerance; however, and the mechanism(s) involved are unknown. Thus, this study tested the hypothesis that age‐dependent increases in fat program glucose intolerance in female IUGR due to alterations in the glucose sensor. Insulin release in response to an oral glucose tolerance test (OGTT), an insulin tolerance test (ITT) and pancreatic glucose transporter 2 (GLUT2) protein expression were measured at one year of age in female control and IUGR rats. Female IUGR demonstrated a significant impairment in glucose tolerance associated with a delay and marked reduction in insulin release (P<0.05); an ITT revealed that female IUGR had higher insulin sensitivity (P<0.05). Although pancreas weight did not differ, pancreatic GLUT2 protein expression adjusted to β‐actin was approximately 4‐fold lower (P<0.05) in IUGR versus control. Thus, the underlying mechanism of impaired metabolic health in female IUGR may involve a decrease in pancreatic GLUT2 expression resulting in a reduction in glucose‐simulated insulin secretion in response to elevated blood glucose leading to glucose intolerance. HL074927; HL51971; AHA12POST11980021.