title: Taurine increases glucose sensitivity of UCP2-overexpressing beta-cells by ameliorating mitochondrial metabolism.
abstract: 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.
authors.affiliation: Dept. of Physiology, Keimyung University School of Medicine, 194, Dongsan-Dong, Jung-Gu, Daegu 700-712, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Bae
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
authors.forename: Chi-Heum
authors.initials: CH
authors.lastname: Cho
authors.forename: Jeong-Geun
authors.initials: JG
authors.lastname: Lim
authors.forename: Seong-Il
authors.initials: SI
authors.lastname: Suh
authors.forename: Taeg-Kyu
authors.initials: TK
authors.lastname: Kwon
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Park
authors.forename: Shin Young
authors.initials: SY
authors.lastname: Ryu
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Ho
authors.forename: Yung-E
authors.initials: YE
authors.lastname: Earm
authors.forename: Dae-Kyu
authors.initials: DK
authors.lastname: Song
mesh_terms: 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
chemical_list: 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