Restriction of protein calories during stages of immaturity has a major influence on glucose metabolism and increases the risk of type 2 diabetes in adulthood. However, it is known that reduction of food intake alleviates insulin resistance. We previously demonstrated an improved insulin-induced glucose uptake in skeletal muscle of chronically undernourished adult rats. The purpose of this work is to investigate whether this condition is present during suckling, a period characterized by physiological insulin resistance, while elucidating some of the underlying mechanisms.

With this aim, 10-day-old pups from food-restricted dams were studied. We showed that undernourished suckling rats are glucose normotolerants, despite their depressed insulin secretion capacity. The content of the main glucose transporters in muscle, GLUT-4 and GLUT-1, was not affected by undernutrition, but fractionation studies showed an improved insulin-stimulated GLUT-4 translocation. p38MAPK protein, implicated in up-regulation of intrinsic activity of translocated GLUT-4, was increased. These changes suggest an improved insulin-induced glucose uptake associated with undernutrition.

Insulin receptor content was increased by food restriction, as well as that of both regulatory and catalytic phosphoinositol 3-kinase subunits. IRS-1 associated PI 3-kinase activity following insulin was enhanced in undernourished rats, as was phospho-GSK 3, in line with insulin hypersensitivity. Surprisingly, PTP1B association with insulin receptor was also increased by undernutrition. These adaptations to a condition of severely limited nutritional resources might result in changes in the development of key tissues and be detrimental later in life, when a correct amount of nutrients is available, as the thrifty phenotype hypothesis predicts.