AMPK α1 mediates the protective effect of adiponectin against insulin resistance in INS-1 pancreatic β cells

The fat-derived protein adiponectin is known to reverse the effects of insulin resistance and to lower blood glucose levels. The AMP-activated protein kinase (AMPK) signalling pathway plays a central role in metabolism and energy homeostasis. Here, to investigate the role of AMPK in the protective effect of adiponectin against insulin resistance, we established the model of high-glucose (HG)- and high-lipid (HL)-induced insulin resistance in INS-1 pancreatic beta cells. We found that 25mM of glucose and 0.4mM of palmitic acid treatment significantly increased cell apoptosis and impaired insulin secretion in INS-1 cells. However, recombinant human adiponectin dramatically reduced HG- and/or HL-induced cell apoptosis and greatly improved insulin secretion. Interestingly, adiponectin treatment also activated AMPK signalling pathway by increasing the phosphorylation of Thr172 in the AMPK alpha subunit; 10 mu M of compound C, a potent AMPK inhibitor, blocked the protective effects of adiponectin against HG/HL-induced insulin resistance. Furthermore, knockout experiments by CRISPR/Cas9 technology showed that AMPK alpha 1, but not AMPK alpha 2, is involved in the protective effects of adiponectin. Taken together, adiponectin reversed the effects of insulin resistance via AMPK alpha 1, which provides a novel insight into the protective mechanism of adiponectin and may be used as a new strategy for the treatment of type 2 diabetes. Significance of the Study Adiponectin can reverse the effects of insulin resistance and lower blood glucose levels. Here, adiponectin reduced HG/HL-induced cell apoptosis and greatly improved insulin secretion. These effects were blocked by AMPK inhibitor, compound C. Specifically, we found that AMPK alpha 1, but not AMPK alpha 2, mediates the protective effects of adiponectin, which provides a novel insight into the protective mechanism of adiponectin against insulin resistance.