Enhancing effect of taurine on glucose response in UCP2-overexpressing beta cells

Uncoupling protein 2 (UCP2) is up-regulated in pancreatic beta cells when exposed to long-term high glucose or free fatty acids, which results in impaired glucose-induced insulin secretion (GIIS). We have evaluated whether taurine pretreatment can restore impaired GIIS of beta cells overexpressing UCP2 by adenovirus (Ad)-mediated transfection technique. In Ad-Null control cells, externally applied glucose (10 mM) inhibited ATP-sensitive potassium (K-ATP) channel activity even in the presence of 300 muM diazoxide. In Ad-UCP2 cells, however, glucose failed to inhibit K-ATP channel activity; despite the response of K-ATP channel itself to glibenclamide was normal. The glucose-stimulated increase of cytosolic Ca2+ concentration ([Ca2+]c) and insulin secretion was also diminished (P < 0.05). When taurine (3 mM) was pretreated for 24 h, the glucose responses of Ad-UCP2 cells were remarkably restored. The effect of taurine was, however, blocked by CCCP (carbonyl cyanide p-chlorophenylhydrazone; 2 muM), a mitochondrial Ca2+ uniporter inhibitor. These results suggest that taurine restores impaired GIIS in Ad-UCP2 cells, at least partially, by acting on the mechanism for Ca2+ sequestration into the mitochondrial matrix. (C) 2004 Elsevier Ireland Ltd. All rights reserved.