Abstract: This invention is directed to a general method for the chronic treatment, potential cure, or prevention of various metabolic and related diseases in people, including diabetes, by modulating IRS2 activity in cells and tissues in the body. IRS1 and IRS2 are part of the insulin or insulin-like growth factor signaling pathway. By upregulating the levels or functional activity of IRS2, insuling is used more efficiently by the body to control nutrient levels. By upregulating IRS2 levels or functional activity in pancreatic ?-cells, glucose sensing and insulin secretion are enhanced.