It was recently shown that leptin impairs insulin signalling, i. e. insulin receptor autophosphorylation and insulin-receptor substrate (IRS)-1 phosphorylation in rat-1 fibroblasts, NIH3T3 cells and HepG2 cells. To evaluate whether leptin might impair the effects of insulin in muscle tissue we studied the interaction of insulin and leptin in a muscle cell system, i. e. C₂C₁₂ myotubes. Preincubation of C₂C₁₂ cells with leptin (1–500 ng/ml) did not significantly affect insulin stimulated glucose transport and glycogen synthesis (1.8 to 2 fold stimulation); however, leptin by itself (1 ng/ml) was able to mimic approximately 80–90 % of the insulin effect on glucose transport and glycogen synthesis. Both glucose transport as well as glycogen synthesis were inhibited by the phosphatidylinositol-3 (PI3)-kinase inhibitor wortmannin and the protein kinase C inhibitor H7 while no effect was observed with the S6-kinase inhibitor rapamycin. We determined whether the effect of leptin occurs through activation of IRS-1 and PI3-kinase. Leptin did not stimulate PI3-kinase activity in IRS-1 immunoprecipitates; however, PI3-kinase activation could be demonstrated in p85α immunoprecipitates (3.04 ± 1.5 fold of basal). In summary the data provide the first evidence for a positive crosstalk between the signalling chain of the insulin receptor and the leptin receptor. Leptin mimics in C₂C₁₂ myotubes insulin effects on glucose transport and glycogen synthesis most likely through activation of PI3-kinase. This effect of leptin occurs independently of IRS-1 activation in C₂C₁₂ cells. [Diabetologia (1997) 40: 606–609]

There is still some controversy concerning the effects of metformin in the treatment of Polycystic Ovary Syndrome (PCOS). The aim of this study was to asses the effect of metformin on clinical, metabolic and hormone parameters in obese women with PCOS. Thirty obese, non-diabetic women with PCOS received 500 mg of metformin or placebo, TID, over 90 days. Assessed parameters included body mass index, waist-to-hip ratio, blood pressure, FSH, LH, total testosterone, SHBG, fasting insulinemia, insulin-to-glucose ratio, total, HDL and LDL cholesterol, triglycerides, and menstrual cycles before and after the use of the drugs. Before treatment, patients did not differ in the two groups. After 90 days of metformin use, PCOS women presented significantly lower levels of total testosterone (p = 0.030) and total cholesterol (p = 0.023) compared to the women that used placebo. The other parameters did not differ between the groups. In conclusion, obese women with PCOS may benefit from the use of metformin through the reduction of hyperandrogenemia, total cholesterol, and possibly by restoration of regular menstrual cycles. Further studies with longer follow-ups are necessary to determine cardiovascular and endometrial metformin benefits and insulin-resistance decrease in women with polycystic ovary syndrome.