In combination with the antagonizing effect of leptin on hepatic insulin signalling under hyperinsulinemia conditions, such as obesity or ageing, determined by oral glucose tolerance tests and hyperinsulinemic-euglycemic clamp tests28,30, it is suspected that leptin/STAT3/Fetuin B may function as a novel adipose-liver axis in vivo to regulate obesity-induced insulin resistance that will ultimately lead to metabolic disorders. The gene discussed is INS; the disease is metabolic disease.