During exploring the interactions and functions of SIRT1 and its target proteins in the development of insulin resistance, the reduced expression of SIRT1 and PGC‐1α is observed in pancreatic β cells of Sprague Dawley (SD) rats with insulin resistance induced by high‐glucose and high‐fat diet, while caloric restriction stimulates the expression of SIRT1 and PGC‐1α. Here, SIRT1 is linked to Insulin resistance.