The role of adipocyte CREB in insulin resistance

Abstract

Obesity is a major public health problem. Dysregulation of lipid metabolism can result in an increase in plasma FFAs and lipid accumulation. Eventually these changes could lead to dyslipidemia, impaired glucose tolerance and insulin resistance, ultimately contributing to the development of type 2 diabetes mellitus. However, the role of the adipose tissue in insulin resistance is unclear. Therefore we would like to discuss the role of adipocyte CREB in insulin resistance. CREB is a cAMP-responsive activator which promotes cellular gene transcription. Together with its coactivators CBP/p300 and TORC2/CRTC2, CREB induces gluconeogenic gene expression in the adipose tissue and the liver. Under obese conditions, CREB is activated, leading to a decrease in the glucose uptake in the adipocytes and a decrease in adiponectin levels, resulting in hyperglycaemia and an increase in FFA levels, enhancing insulin resistance. Further analysis of the CREB pathway and studies of the CBP/p300 and the TORC2/CRTC2 pathway could provide more insight into the hormone regulated pathways in adipocytes under obese conditions. This could eventually lead to the development of a specifically targeted medicine and a better treatment of type 2 diabetes mellitus in obesity.