The effect of metformin treatment on the basal and gonadotropin-stimulated steroidogenesis in male rats with type 2 diabetes mellitus.

Type 2 diabetes mellitus impairs reproductive functions in men, and important tasks are deciphering the mechanisms of testicular dysfunctions in diabetes and the search of effective approaches to their correction. The purpose was to study the effect of four-week metformin treatment (120 mg kg-1  day-1 ) of male Wistar rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes on basal and gonadotropin-stimulated steroidogenesis, intratesticular content of leptin and the leptin and luteinising hormone receptors and on spermatogenesis. Diabetic rats had hyperleptinaemia, androgen deficiency and reduced sperm count and quality, and in the testes, they had the increased leptin level and the decreased content of the leptin and luteinising hormone receptors and 17-hydroxyprogesterone. The stimulating effects of chorionic gonadotropin on testosterone production and expression of steroidogenic genes (Star, Cyp11a1) were decreased. Metformin restored basal and gonadotropin-stimulated blood testosterone levels. In the testes, it restored gonadotropin-stimulated 17-hydroxyprogesterone, androstenedione and testosterone levels, Star expression and the content of leptin and the leptin and luteinising hormone receptors. Metformin also improved epididymal sperm count and morphology. We concluded that metformin treatment normalises the testicular steroidogenesis in diabetic rats, which is due to restoration of the gonadotropin and leptin systems in the testes and is associated with an improvement in spermatogenesis.

The Effect of Long-Term Intranasal Serotonin Treatment on Metabolic Parameters and Hormonal Signaling in Rats with High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes.

In the last years the treatment of type 2 diabetes mellitus (DM2) was carried out using regulators of the brain signaling systems. In DM2 the level of the brain serotonin is reduced. So far, the effect of the increase of the brain serotonin level on DM2-induced metabolic and hormonal abnormalities has been studied scarcely. The present work was undertaken with the aim of filling this gap. DM2 was induced in male rats by 150-day high-fat diet and the treatment with low dose of streptozotocin (25 mg/kg) on the 70th day of experiment. From the 90th day, diabetic rats received for two months intranasal serotonin (IS) at a daily dose of 20 µg/rat. The IS treatment of diabetic rats decreased the body weight, and improved glucose tolerance, insulin-induced glucose utilization, and lipid metabolism. Besides, it restored hormonal regulation of adenylyl cyclase (AC) activity in the hypothalamus and normalized AC stimulation by ß-adrenergic agonists in the myocardium. In nondiabetic rats the same treatment induced metabolic and hormonal alterations, some of which were similar to those in DM2 but expressed to a lesser extent. In conclusion, the elevation of the brain serotonin level may be regarded as an effective approach to treat DM2 and its complications.