Protein Deficiency and Nutritional Recovery Modulate Insulin Secretion and the Early Steps of Insulin Action in Rats

Manuscript received 2 March 1998. Initial reviews completed 15 April 1998. Revision accepted 10 July 1998.

Márcia Q. Latorraca^*, , Marise A. B. Reis^*, Everardo M. Carneiro, Maria A. R. Mello, Licio A. Velloso^**, Mario J. A. Saad^**, and A. Carlos Boschero^*,

^* Departamento de Fisiologia e Biofisica, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, Campinas, São Paulo 13083-970, Brasil,  Departamento de Educação Física, Instituto de Biociências, Universidade Estadual Paulista, UNESP, Rio Claro, São Paulo 13506-900, Brasil and ^** Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, UNICAMP, Campinas, São Paulo, 13081-970, Brasil

Maternal malnutrition was shown to affect early growth and leads to permanent alterations in insulin secretion and sensitivity of offspring. In addition, epidemiological studies showed an association between low birth weight and glucose intolerance in adult life. To understand these interactions better, we investigated the insulin secretion by isolated 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% protein [low (LP) protein] during fetal life, suckling and after weaning, and in rats receiving 6% protein during fetal life and suckling followed by a 17% protein diet after weaning (recovered). The basal and maximal insulin secretion by islets from rats fed LP diet and the basal release by islets from recovered rats were significantly lower than that of control rats. The dose-response curves to glucose of islets from LP and recovered groups were shifted to the right compared to control 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 phosphorylation and the association between insulin receptor substrate-1 and phosphatidylinositol 3-kinase were greater in rats fed a LP diet than in control rats. In recovered rats, these variables were not significantly different from those of the other two groups. These results suggest that glucose homeostasis is maintained in LP and recovered rats by an increased sensitivity to insulin as a result of alterations in the early steps of the insulin signal transduction pathway.

The Journal of Nutrition Vol. 128 No. 10 October 1998, pp. 1643-1649
Copyright ©1998 by the American Society for Nutritional Sciences

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