Exposure of the Pregnant Rat to Low Protein Diet Causes Impaired Glucose Homeostasis in the Young Adult Offspring by Different Mechanisms in Males and Females

Abstract

The understanding of the mechanisms by which gender dimorphisms are involved in the modulation of insulin sensitivity and glucose tolerance can be crucial to unravel the development of type 2 diabetes. Rats treated with a low protein diet (LP, 8% protein content) during pregnancy and lactation have a reduced β-cell mass at birth and a reduced insulin secretion at weaning. In this study we examined the effect of LP diet on glucose homeostasis from birth to adulthood when offspring previously exposed to LP were subsequently switched to control diet (C, 20% protein content) at weaning. The LP group had a reduced body weight after weaning compared to the C-fed rats, although their food intake was not significantly different. Furthermore, LP males had a significant increase in visceral adiposity relative to their body weight ( P < 0.05). Intraperitoneal glucose tolerance test (IGTT) showed that glucose clearance was unchanged until 130 days of age when LP-fed females showed elevated blood glucose compared to C, despite similar plasma insulin levels. Females also demonstrated a significant reduction in mean pancreatic islet number, individual islet size and beta cell mass. However, no differences in IGTT or islet morphometry were observed in LP males, although basal insulin levels were twofold higher. Akt phosphorylation in response to insulin was reduced in adipose and skeletal muscle of adult rats following exposure to LP diet in early life when compared to control-fed animals, but this was only apparent in males. Plasma testosterone levels were also reduced in males at 130 days age. These data suggest that the development of impaired glucose homeostasis in offspring of LP-fed rats is likely to occur by different mechanisms in males and females.