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 [Rb-86(+)] efflux in both K-ATP channel types in the presence of metabolic inhibitors, which was confirmed by electrophysiological techniques. The [Rb-86(+)] 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. (C) 1999 Elsevier Science B.V. All rights reserved.