Effects of protein malnutrition on glucose tolerance in rats with alloxan-induced diabetes

Protein-calorie malnutrition produces glucose intolerance and reduced insulin release in response to glucose. Rats adapted to low- or high-protein diets show an increased resistance to the diabetogenic action of a single dose of streptozotocin or alloxan. To determine the effects of dietary protein level on pancreatic function, we measured serum glucose levels under basal conditions and during the oral glucose tolerance test (GTT) performed before and after a single dose of alloxan administered to rats fed a 25% or a 6% protein diet for a period of 8 weeks. The incidence of mild hyperglycemia (serum glucose > 250 mg/dl) was greater among the rats fed the 25% protein diet (81%) than among those fed the 6% protein diet (42%). During the GTT performed before alloxan administration the serum glucose levels of the rats fed the 6% protein diet were not found to be significantly different from those of rats fed the 25% protein diet. During the GTT performed after alloxan injection all rats showed intolerance to the substrate (serum glucose > 160 mg/dl 120 min after glucose administration) regardless of whether basal serum glucose was normal or high. In summary, alloxan was less effective in producing basal hyperglycemia in the rats fed the 6% protein diet than in those fed the 25% protein diet but caused glucose intolerance during the oral GTT in both groups. Thus, it seems that feeding a 6% protein diet to rats offers only partial protection against the toxic effects of alloxan.

Functional alterations in endocrine pancreas of rats with different degrees of dexamethasone-induced insulin resistance

Objectives: We have analyzed the peripheral insulin and glucose sensitivity in vivo, and islet function ex vivo in rats with different degrees of insulin resistance induced by dexamethasone (DEX).Methods: Dexamethasone, in the concentrations of 0.1 (DEX 0.1), 0.5 (DEX 0.5), and 1.0 mg/kg body weight (DEX 1.0) was administered daily, intraperitoneally, to adult Wistar rats for 5 days, whereas controls received saline.Results: Dexamethasone treatment induced peripheral insulin resistance in a dose-dependent manner. At the end of the treatment, only DEX 1.0 rats showed significant increase of postabsorptive blood glucose and serum triglycerides, and nonesterified fatty acids levels. Incubation of pancreatic islets in increasing glucose concentrations (2.8-22 mM) led to an augmented insulin secretion in all DEX-treated rats. Leucine, carbachol, and high KCl concentrations induced the insulin release in DEX 0.5 and DEX 1.0, whereas arginine augmented secretion in all DEX-treated groups.Conclusions: We demonstrate that in DEX 0.5 and, especially in DEX 0.1 groups, but not in DEX 1.0, the adaptations that occurred in the endocrine pancreas are able to counteract metabolic disorders (glucose intolerance and dyslipidemia). These animal models seem to be interesting approaches for the study of degrees of subjacent effects that may mediate type 2 diabetes (DEX 1.0) and islet function alterations, without collateral effects (DEX 0.1 and DEX 0.5).

Morphofunctional Alterations in Endocrine Pancreas of Short- and Long-term Dexamethasone-treated Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)