Taurine increases glucose sensitivity of UCP2-overexpressing beta-cells by ameliorating mitochondrial metabolism.
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 Ca(2+) increase was significantly ameliorated by taurine. A mitochondrial Ca(2+) 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 Ca(2+) influx through the Ca(2+) uniporter, thereby enhancing mitochondrial metabolic function and increasing the ATP/ADP ratio.
Han
Jin
J
Dept. of Physiology, Keimyung University School of Medicine, 194, Dongsan-Dong, Jung-Gu, Daegu 700-712, Korea.
Bae
Jae Hoon
JH
Kim
So-Yeon
SY
Lee
Hyun-Young
HY
Jang
Byeong-Churl
BC
Lee
In-Kyu
IK
Cho
Chi-Heum
CH
Lim
Jeong-Geun
JG
Suh
Seong-Il
SI
Kwon
Taeg-Kyu
TK
Park
Jong-Wook
JW
Ryu
Shin Young
SY
Ho
Won-Kyung
WK
Earm
Yung-E
YE
Song
Dae-Kyu
DK
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007473:Ion Channels; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000502:physiology*; D014162:Transfection; D000071246:Uncoupling Protein 2
D007328:Insulin; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D015221:Potassium Channels; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D013654:Taurine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005947:Glucose; D002118:Calcium