The mechanism of phenylbutyric acid-induced glucose uptake in 3T3-L1 adipocytes

Abstract

Diabetes Mellitus is a chronic metabolic disease characterized by impaired glucose uptake and hyperglycemia. The impaired glucose uptake in adipocytes results from defects in insulin secretion and/or action. Phenylbutyric Acid (PBA), a short chain fatty acid, was found to increase glucose uptake in differentiated 3T3-L1 cells. The purpose of this study is to investigate the mechanism of this PBA-induced glucose uptake. Our findings suggest that PBA neither alters the viability nor the reactive oxygen species production of differentiated 3T3-L1 cells. PBA increases the plasma membrane abundance of the glucose transporter GLUT4 without a significant increase in its total protein expression. Alternatively, the total GLUT1 protein expression increase significantly in PBA-treated adipocytes compared to control. PBA reduces the activity of PTEN (a PI3-kinase pathway inhibitor) through phosphorylation of PTEN. Concomitantly, there is a significant increase in PIP3 and activation of Akt, as evident by its phosphorylation in the PBA-treated adipocytes. Our data suggest that PBA induces glucose uptake in 3T3-L1 adipocytes through affecting the expression of glucose transporters and/or their trafficking possibly via the PI3-kinase pathway. This offers PBA, or its modulators, as potential prospect targets for the management of Diabetes Mellitus.