Neonatal streptozotocin-induced diabetes mellitus: a model of insulin resistance associated with loss of adipose mass.

The use of experimental models of diabetes mellitus (DM) has been useful in understanding the complex pathogenesis of DM. Streptozotocin (STZ) injected in rats during the neonatal period has usually led to the major features described in diabetic patients (hyperglycemia, polyphagia, polydipsia, polyuria, and abnormal glucose tolerance) in a short period. Diabetes mellitus is a product of low insulin sensibility and pancreatic beta-cell dysfunction. Its process is characterized by a symptomless prediabetic phase before the development of the disease. In this study, we investigated the long-term effects of diabetes induction regarding the cellular metabolic aspects of this model and its similarities with diabetes found in humans. Male Wistar rats (5-day old) were intraperitoneally injected with STZ (150 mg/kg) and followed up for 12 weeks. On the 12th week, animals were decapitated and peri-epididymal fat pads were excised for adipocyte isolation. The following studies were performed: insulin-stimulated 2-deoxy-d-[(3)H]glucose uptake; incorporation of d-[U-(14)C]-glucose into lipids and conversion into (14)CO(2); and insulin binding. The weight gain rate of the STZ-treated group became significantly lower by the eighth week. These rats developed polyphagia, polydipsia, polyuria, and glycosuria, and impaired glucose tolerance. Biological tests with isolated adipocytes revealed a reduction in the insulin receptor number and an impairment in their ability to oxidize glucose as well as to incorporate it into lipids. Interestingly, parallel to reduced body weight, the adipocyte size of STZ rats was significantly small. We concluded that apart of a decrease in pancreatic insulin content, this experimental model of DM promotes a remarkable and sustained picture of insulin resistance in adulthood that is strongly related to a loss in adipose mass.

Endurance exercise training increases insulin responsiveness in isolated adipocytes through IRS/PI3-kinase/Akt pathway.

Endurance exercise training promotes important metabolic adaptations, and the adipose tissue is particularly affected. The aim of this study was to investigate how endurance exercise training modulates some aspects of insulin action in isolated adipocytes and in intact adipose tissue. Male Wistar rats were submitted to daily treadmill running (1 h/day) for 7 wk. Sedentary age-matched rats were used as controls. Final body weight, body weight gain, and epididymal fat pad weight did not show any statistical differences between groups. Adipocytes from trained rats were smaller than those from sedentary rats (205 +/- 16.8 vs. 286 +/- 26.4 pl; P < 0.05). Trained rats showed decreased plasma glucose (4.9 +/- 0.13 vs. 5.3 +/- 0.07 mM; P < 0.05) and insulin levels (0.24 +/- 0.012 vs. 0.41 +/- 0.049 mM; P < 0.05) and increased insulin-stimulated glucose uptake (23.1 +/- 3.1 vs. 12.1 +/- 2.9 pmol/cm(2); P < 0.05) compared with sedentary rats. The number of insulin receptors and the insulin-induced tyrosine phosphorylation of insulin receptor-beta subunit did not change between groups. Insulin-induced tyrosine phosphorylation insulin receptor substrates (IRS)-1 and -2 increased significantly (1.57- and 2.38-fold, respectively) in trained rats. Insulin-induced IRS-1/phosphatidylinositol 3 (PI3)-kinase (but not IRS-2/PI3-kinase) association and serine Akt phosphorylation also increased (2.06- and 3.15-fold, respectively) after training. The protein content of insulin receptor-beta subunit, IRS-1 and -2, did not differ between groups. Taken together, these data support the hypothesis that the increased adipocyte responsiveness to insulin observed after endurance exercise training is modulated by IRS/PI3-kinase/Akt pathway.