Troglitazone but not pioglitazone affects ATP-sensitive K(+) channel activity.
We compared the effects of the two thiazolidinedione derivatives, troglitazone and pioglitazone, on ATP-sensitive K(+) (K(ATP)) channel activities. Pancreatic beta-cell type and cardiac type K(ATP) channels were reconstituted in COS-1 cells (SV 40-transformed African green monkey kidney (AGMK) cells) by heterologously expressing sulfonylurea receptor 1 (SUR1) plus Kir6.2 and sulfonylurea receptor 2A (SUR2A) plus Kir6.2, respectively. Troglitazone inhibited [86Rb(+)] efflux in both K(ATP) channel types in the presence of metabolic inhibitors, which was confirmed by electrophysiological techniques. The [86Rb(+)] efflux increased by the channel openers diazoxide and pinacidil was abolished by troglitazone. In contrast, pioglitazone did not affect these channel activities in either type K(ATP) channel. These results suggest that troglitazone modulates the various cellular functions including insulin secretion by inhibiting the K(ATP) channels, while pioglitazone has no effect on K(ATP) channel activity.
Sunaga
Y
Y
Department of Metabolism and Clinical Nutrition, Kyoto University Graduate School of Medicine, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan.
Inagaki
N
N
Gonoi
T
T
Yamada
Y
Y
Ishida
H
H
Seino
Y
Y
Seino
S
S
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D019556:COS Cells; D002839:Chromans / Q000494:pharmacology*; D003981:Diazoxide / Q000494:pharmacology; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D020110:Pinacidil / Q000494:pharmacology; D000077205:Pioglitazone; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D012414:Rubidium Radioisotopes / Q000378:metabolism; D064233:Sulfonylurea Receptors; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014162:Transfection; D000077288:Troglitazone
D018528:ATP-Binding Cassette Transporters; D002839:Chromans; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D011993:Recombinant Fusion Proteins; D012414:Rubidium Radioisotopes; D064233:Sulfonylurea Receptors; D013844:Thiazoles; D045162:Thiazolidinediones; D020110:Pinacidil; D000255:Adenosine Triphosphate; D000077288:Troglitazone; D003981:Diazoxide; D005905:Glyburide; D000077205:Pioglitazone