Insulin sensitivity in adult female rats subjected to malnutrition during the perinatal period

Abstract

Objective: The purpose of the present study was to investigate insulin sensitivity in adult rats after perinatal malnutrition.

Methods: Wistar rats were food-restricted (about 50% of normal food intake) during pregnancy (group A) or during pregnancy and lactation (group B) and compared with rats fed ad libitum during pregnancy and lactation (group C). The insulin sensitivity in the adult female offspring was assessed with the hyperinsulinemic euglycemic clamp technique in combination with isotopic measurement of glucose turnover. Hepatic and peripheral insulin sensitivities were determined in the basal state and after 3, 10, or 50 mU/kg/minute insulin.

Results: Group A and group B rats had lower non-fasting plasma insulin levels (0.15 +/- 0.07 and 0.15 +/- 0.01 nmol/L, respectively) than group C rats (0.26 +/- 0.03 nmol/L) (P < .001). During hyperinsulinemia, the steady-state glucose infusion rate was lower in groups A and B, with 10 and 50 mU/kg/minute insulin, indicating insulin resistance. Hepatic glucose production in the basal state was normal, but its suppression by 10 and 50 mU/kg/minute insulin was dampened in group A and B rats, indicating decreased insulin responsiveness of the liver. Peripheral glucose utilization, however, in the basal state and during hyperinsulinemia remained normal in groups A and B.

Conclusion: After perinatal malnutrition, adult rats have decreased plasma insulin concentrations and exhibit insulin resistance, with decreased insulin responsiveness of the liver.