Taurine increases glucose sensitivity of UCP2-overexpressing β-cells by ameliorating mitochondrial metabolism

Abstract

A low-taurine diet during fetal or early postnatal life causes abnormal pancreatic β-cell development. Tissue and plasma taurine concentrations can also be low in diabetic patients. We examined the effect of taurine on impaired glucose responses in diabetic rat β-cells adenovirally overexpressing uncoupling protein (UCP)2, which is upregulated in obesity-related type 2 diabetes. We found that taurine pretreatment restored the ATP-to-ADP (ATP/ADP) ratio and glucose-stimulated insulin secretion in UCP2-infected islets. ATP-sensitive K+ channel sensitivity to dihydroxyacetone, another insulin secretagogue, was similar in both UCP2-infected and control β-cells. In freshly isolated mitochondria from UCP2-overexpressing insulin-secreting (INS)-1 β-cells, methyl pyruvate-mediated mitochondrial Ca2+ increase was significantly ameliorated by taurine. A mitochondrial Ca2+ uniporter blocker, ruthenium red, inhibited the action of taurine. This study suggests that taurine enhances the glucose sensitivity of UCP2-overexpressing β-cells, probably by increasing mitochondrial Ca2+ influx through the Ca2+ uniporter, thereby enhancing mitochondrial metabolic function and increasing the ATP/ADP ratio.