IRS1 and Hyperinsulinemia: Accordingly, we have recently addressed that the treatment with enhancers of insulin activity, although in a model of diet-induced hyperadiposity, was effective in preventing hyperinsulinemia, dyslipidemia, hypertrophic expansion of abdominal adipose tissue mass, and adipocyte leptin mRNA overexpression, whose mechanisms were mainly mediated by the improvement of both IRS-1 and IRS-2 functionalities after metformin [39].