Evaluation of Glucose Uptake and Uncoupling Protein 1 Activity in Adipose Tissue of Diabetic Mice upon β-Adrenergic Stimulation.

Abstract

Regulation of metabolic activity in adipose tissue is of great concern for treating obesity. This study aimed to evaluate the adrenergic regulation of glucose uptake and the thermogenic program in adipose tissues in mouse models of both type 1 and 2 diabetes mellitus (DM). Male mice were treated with streptozotocin to induce type 1 (T1) DM, and obese ob/ob mice were used for the type 2 (T2) DM model. After selective β3-adrenoreceptor stimulation by CL 316,243 (CL) treatment, 2-deoxy-D-[14C]glucose ([14C]DG) was administered to DM and corresponding control mice. Radioactivity and uncoupling protein 1 (UCP1) expression were measured and analyzed in adipose tissues. In T1DM, [14C]DG uptake in brown adipose tissue (BAT) decreased both at rest and upon CL stimulation, and UCP1 expression was preserved. However, CL treatment enhanced [14C]DG uptake without impairing UCP1 expression in inguinal white adipose tissue (iWAT). In this model, CL could not alter blood glucose levels. In T2DM mice, the blood glucose level was significantly lowered by CL treatment. There was no decrease in CL-induced [14C]DG uptake in BAT, and UCP1 expression was maintained. However, [14C]DG uptake was not increased in iWAT and no UCP1 expression was observed in iWAT (browning). The metabolic response against adrenergic stimulation varied depending on the type of adipose tissue and DM. This could be important for the therapeutic activation of adipose tissue metabolism in obese diabetic patients.