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Am J Physiol Endocrinol Metab 287: E1008-E1018, 2004. First published July 20, 2004; doi:10.1152/ajpendo.00008.2004
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Taurine increases glucose sensitivity of UCP2-overexpressing {beta}-cells by ameliorating mitochondrial metabolism

Jin Han,4,* Jae Hoon Bae,1,* So-Yeon Kim,1 Hyun-Young Lee,1 Byeong-Churl Jang,2 In-Kyu Lee,2 Chi-Heum Cho,2 Jeong-Geun Lim,2 Seong-Il Suh,2 Taeg-Kyu Kwon,2 Jong-Wook Park,2 Shin Young Ryu,3 Won-Kyung Ho,3 Yung-E Earm,3 and Dae-Kyu Song1,2

1Department of Physiology, 2Chronic Disease Research Center, Keimyung University School of Medicine, Daegu 700-712; 3Department of Physiology, College of Medicine, Seoul National University, Seoul 110-799; and 4Department of Physiology and Biophysics, College of Medicine, Inje University, Busanjin-Gu, Busan 614-735, Korea

Submitted 7 January 2004 ; accepted in final form 18 July 2004

A low-taurine diet during fetal or early postnatal life causes abnormal pancreatic {beta}-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 {beta}-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 {beta}-cells. In freshly isolated mitochondria from UCP2-overexpressing insulin-secreting (INS)-1 {beta}-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 {beta}-cells, probably by increasing mitochondrial Ca2+ influx through the Ca2+ uniporter, thereby enhancing mitochondrial metabolic function and increasing the ATP/ADP ratio.

insulin; ATP-sensitive K+ channel; mitochondrial Ca2+; ATP-to-ADP ratio; pancreatic islets; uncoupling protein 2


Address for reprint requests and other correspondence: D.-K. Song, Dept. of Physiology, Keimyung Univ. School of Medicine, 194, Dongsan-Dong, Jung-Gu, Daegu 700-712, Korea (E-mail: dksong{at}kmu.ac.kr)






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