Impairment of insulin signaling in hepatocytes by supernatants of insulin-activated macrophages

Background: Hepatic insulin resistance and hyperinsulinemia are hallmarks in pre-diabetic obese patients. It is generally assumed that hyperinsulinemia is a consequence of the attempt of the body to compensate insulin resistance by enhanced release of insulin from β-cells. Here, evidence is provided that hyperinsulinemia itself might contribute to the development of hepatic insulin resistance by enhancing cytokine production in macrophages. Methods: U937 cells were differentiated into macrophages by PMA treatment. These macrophages were stimulated with 100 nM insulin for 24h and cytokine gene expression was dete…