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 microM 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 microM), 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.
Lee
Sang-Hoon
SH
Department of Physiology, Keimyung University School of Medicine 194, Dongsan-Dong, Jung-Gu, Daegu 700-712, Republic of Korea.
Sang-Hoon
Lee
L
Lee
Hyun-Young
HY
Hyun-Young
Lee
L
Kim
So-Yeon
SY
So-Yeon
Kim
K
Lee
In-Kyu
IK
In-Kyu
Lee
L
Song
Dae-Kyu
DK
Dae-Kyu
Song
S
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000502:physiology; D000256:Adenoviridae; D000818:Animals; D002118:Calcium / Q000502:physiology; D003600:Cytosol / Q000502:physiology; D004594:Electrophysiology; D005822:Genetic Vectors; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007473:Ion Channels; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D054086:KATP Channels; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000494:pharmacology*; D014475:Uncoupling Agents / Q000494:pharmacology; D000071246:Uncoupling Protein 2
D018528:ATP-Binding Cassette Transporters; D007328:Insulin; D007473:Ion Channels; D054086:KATP Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D024661:Potassium Channels, Inwardly Rectifying; C000604391:Ucp2 protein, rat; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2; C092520:uK-ATP-1 potassium channel; D013654:Taurine; D005947:Glucose; D005905:Glyburide; D002118:Calcium