PROTEIN-DEFICIENCY AND NUTRITIONAL RECOVERY MODULATE INSULIN-SECRETION AND THE EARLY STEPS OF INSULIN ACTION IN RATS

Maternal malnutrition was shown to affect early growth and leads to pe rmanent alterations in insulin secretion and sensitivity of offspring. In addition, epidemiological studies showed an association between lo w birth weight and glucose intolerance in adult life. To understand th ese interactions better, we investigated the insulin secretion by isol ated islets and the early events related to insulin action in the hind -limb muscle of adult rats fed a diet of 17% protein (control) or 6% p rotein [low (LP) protein] during fetal life, suckling and after weanin g, and in rats receiving 6% protein during fetal life and suckling fol lowed by a 17% protein diet after weaning (recovered). The basal and m aximal insulin secretion by islets from rats fed LP diet and the basal release by islets from recovered rats were significantly lower than t hat of control rats. The dose-response curves to glucose of islets fro m LP and recovered groups were shifted to the right compared to contro l islets, with the half-maximal response (EC50) occurring at 16.9 +/- 1.3, 12.4 +/- 0.5 and 8.4 +/- 0.1 mmol/L, respectively. The levels of insulin receptor, as well as insulin receptor substrate-1 and phosphor ylation and the association between insulin receptor substrate-1 and p hosphatidylinositol 3-kinase were greater in rats fed a LP diet than i n control rats. In recovered rats, these variables were not significan tly different from those of the other two groups. These results sugges t that glucose homeostasis is maintained in LP and recovered rats by a n increased sensitivity to insulin as a result of alterations in the e arly steps of the insulin signal transduction pathway.