IMPAIRED GLUCOSE SENSITIVITY OF ATP-SENSITIVE K+ CHANNELS IN PANCREATIC BETA-CELLS IN STREPTOZOTOCIN-INDUCED NIDDM RATS

ATP-sensitive K+ channels (K(ATP) channels) are known to play a key role in the cellular mechanism of insulin secretion from pancreatic beta-cells. In order to examine the possible impairment of K(ATP) channel function in non-insulin-dependent diabetes mellitus (NIDDM), we have studied the properties of the K(ATP) channels in single beta-cells of neonatally streptozotocin-induced diabetic rats (NSZ rats) using the patch-clamp technique. The unitary conductance of the channel in diabetic beta-cells was virtually identical to that in control beta-cells and there was no difference in the sensitivity to ATP and glibenclamide of K(ATP) channels between the NIDDM and control groups. In response to glucose, the activity of the K(ATP) channels was diminished in a dose-dependent manner in both control and diabetic cells. However, the inhibition of the K(ATP) channels in beta-cells of NSZ rats was significantly less than that in control cells. Even in the presence of 11.1 mM glucose, the openings of a few single K(ATP) channels were consistently observed in cell-attached patch membranes of diabetic, but not control, beta-cells. Thus, it appears that the impaired insulinotropic action of glucose in beta-cells in NSZ rats is associated with a reduced sensitivity of the K(ATP) channel to glucose, but not to ATP, presumably due to a deficiency in glucose metabolism.