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

Abstract

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.

Restoration of insulin secretion in pancreatic islets of protein-deficient rats by reduced expression of insulin receptor substrate (IRS)-1 and IRS-2

“…The present animal model matches all hormonal, biochemical and phenotypic characteristics of those reported in previously published studies (Latorraca et al 1998, Prada et al 2001. The pancreatic islets of protein-deficient rats are smaller and possess fewer insulin granules than islets from eutrophic rats (not shown).…”

“…Several studies have attempted to characterize the molecular mechanisms underlying the impaired response of the pancreatic islets of protein-deficient animals to glucose and other insulinotrophic agents (Rao & Menon 1993, Reis et al 1997, Latorraca et al 1998, Barbosa et al 2002, Ferreira et al 2003. Caloric and protein deficiency produce phenotypic changes in pancreatic islets, which are smaller and composed of a lower number of -cells, than islets of eutrophic animals (Petrik et al 2001).…”

Evaluation of skeletal muscle regeneration in experimental model after malnutrition

“…Escriva et al (1991) observed the body weight gain reduction associated with functional alterations in insulin action in tissues in young rats subjected to protein restriction for four weeks. Latorraca et al (1998) evaluated the offspring of rats undernourished during pregnancy and breastfeeding. The animals exposed to a low protein diet had a reduction in insulin secretion, probably as a consequence of deficient Ca 2+ absorption in pancreatic cells.…”

Regulation of Energy Metabolism of the Heart during Acute Increase in Heart Work

“…The consequences of maternal malnutrition induced by either a low protein diet or caloric restriction during gestation and lactation cause major changes in the structure and function of several organs in the offspring. Pregnant rats fed a low protein diet produced pups with alterations in pancreatic islets (8,9). These include reduced islet vascularization, ␤ cell proliferative capacity, and islet size with rightward shift (decreased sensitivity) in glucose-stimulated insulin secretion and altered sensitivity to insulin in muscle (8,9).…”