Histone deacetylase 6 regulates insulin signaling in pancreatic β cells.

Abstract

The reduction of pancreatic β cell mass is one of the key factors for the onset of type 2 diabetes. Many reports have indicated that insulin signaling is important for type 2 diabetes, but the mechanism by which insulin signaling is altered in pancreatic β cells remains unclear. This study was designed to examine the role of histone deacetylases (HDACs) in the regulation of insulin signaling in pancreatic β cells. We found that insulin signaling was downregulated by inhibition of HDAC6. HDAC6 expression was specifically observed in pancreatic β cells and was decreased in the pancreatic islets of a type 2 diabetes mouse model. When a mouse pancreatic β cell line (MIN6 cells) was treated with palmitic acid to mimic the effect of a high-fat diet on pancreatic β cells, HDAC6 was imported into the nucleus. These results suggest that HDAC6 plays an important role in the regulation of insulin signaling in pancreatic β cells. Therefore, clarifying the regulation of insulin signaling by HDAC6 may be a valuable approach for the treatment of type 2 diabetes.