Some class I antiarrhythmic drugs induce a sporadic hypoglycemia by producing insulin secretion via inhibition of ATP-sensitive K
+ (K
ATP) channels of pancreatic
β-cells. It remains undetermined whether amiodarone produces insulin secretion by inhibiting K
ATP channels. In this study, effects of amiodarone on K
ATP channels, L-type Ca
2+ channel, membrane potential, and insulin secretion were examined and compared with those of quinidine in a
β-cell line (MIN6). Amiodarone as well as quinidine inhibited the openings of the K
ATP channel in a concentration-dependent manner without affecting its unitary amplitude in inside-out membrane patches of single MIN6 cells, and the IC
50 values were 0.24 and 4.9
μM, respectively. The L-type Ca
2+ current was also inhibited by amiodarone as well as quinidine in a concentration-dependent manner. Although glibenclamide (0.1
μM) or quinidine (10
μM) significantly potentiated the insulin secretion from MIN6 cells, amiodarone (1 – 30
μM) failed to increase insulin secretion. Amiodarone (30
μM) and nifedipine (10
μM) significantly inhibited the increase in insulin secretion produced by 0.1
μM glibenclamide. Amiodarone (30
μM) produced a gradual decrease of the membrane potential, but did not produce repetitive electrical activity in MIN6 cells. Glibenclamide (1
μM) produced a slow depolarization, followed by spiking activity which was inhibited by 30
μM amiodarone. Thus, amiodarone is unlikely to produce hypoglycemia in spite of potent inhibitory action on K
ATP channels in insulin-secreting cells, possibly due to its Ca
2+ channel–blocking action.
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