Impaired Glucose Sensitivity of ATP-Sensitive K⁺ Channels in Pancreatic β-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 β 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 β cells of neonatally streptozotocin-induced diabetic rats (NSZ rats) using the patch-clamp technique. The unitary conductance of the channel in diabetic β-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 β-cells of NSZ rats was significantly < 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, β-cells. Thus, it appears that the impaired insulinotropic action of glucose in β-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.