The effect of phenyl butyric acid on glucose uptake in 3T3-L1 adipocytes

Abstract

Diabetes Mellitus is a chronic metabolic disease marked by altered glucose homeostasis and insulin resistance. Insulin signaling and the ensuing glucose uptake may be regulated by variety cellular proteins. The phosphatase PTEN antagonizes the insulin-induced-PI3K-driven cascade that normally leads to GLUT4 membrane translocation. The purpose of this study is to investigate the effect of Phenyl Butyric Acid (PBA), which is a chemical chaperone and a documented stimulator of PARK7 (a known PTEN inhibitor), on glucose uptake and the insulin cascade in differentiated 3T3-L1 adipocytes. Our results indicate that PBA treatment, alone or with insulin induction, significantly increased the glucose uptake in 3T3-L1 adipocytes. As expected, PBA significantly increased PARK7 protein expression, while significantly decreasing p-PTEN protein expression. No change in total GLUT4 expression level was observed with PBA treatment compared to control. PBA did not alter the gross differentiation of the adipocytes, but changed its adipokine profile by decreasing leptin secretion. Our data hint to a possible role for PARK7 in insulin signaling, and reveal PBA as a possible candidate for the ancillary management of type 2 Diabetes.