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Treatment with the NO-synthase inhibitor, methylene blue, moderates the decrease in serum leptin concentration in streptozotocin-induced diabetes.

It was previously reported that serum leptin concentrations were decreased in rats with streptozotocin-induced diabetes. Also, simultaneous nitric oxide (NO)-synthase inhibitor treatment is known to partially attenuate streptozotocin-induced diabetes development. The aim of our study was to investigate the influence of the NO-synthase inhibitor, methylene blue, on serum leptin concentration and diabetes development. Body weight, blood glucose, glycated hemoglobin and leptin concentration were measured in a control group, diabetic (streptozotocin 70 mg/kg i.p.) group, methylene blue (40 mg/kg in the food) treated group and a diabetic group treated with methylene blue. After six weeks of experiments, blood glucose and glycated hemoglobin increased significantly in the diabetic group vs controls (27.31 vs 5.49 mmol.l(-1), 14.11 vs 6.79%, respectively) and this increase was partially attenuated by simultaneous methylene blue treatment (16.8 vs 27.31 mmol/l, p < 0.05). Body weight and serum leptin fell in diabetic rats vs controls (248.9 vs 342.8 g, 0.57 vs 3.46 ng.ml(-1)). Treatment with methylene blue significantly suppressed the drop of body weight and the increase in blood glucose and glycated hemoglobin concentrations in the diabetic group. The decrease of serum leptin levels was significantly inhibited by methylene blue in the first experiment (1.1 vs 0.57 ng. ml(-1), p < 0.05); the same trend was found in a second experiment but the differences did not reach statistical significance. We conclude that the drop of serum leptin levels in diabetic rats is probably mainly due to streptozotocin-induced insulin deficiency, which is partially attenuated by NO-synthase inhibitor treatment.