It is accepted for insulin-secreting cells in culture that the closure of ATP-sensitive K+ channels causes the glucose-dependent depolarization of pancreatic β-cells seen at subthreshold levels (<100 mg/dl) of glucose. The question remains for the more thoroughly studied β-cells in freshly dissected intact islets, however, whether closure of these channels is responsible for subthreshold glucose-dependent depolarization and suprathreshold glucose-dependent regulation of membrane electrical activity. To answer this, we took advantage of the ability of tolbutamide, an orally active antidiabetic agent, to specifically inhibit ATP-sensitive K+ channels in pancreatic β-cells to determine whether these channels are active at sub- and suprathreshold levels of glucose and whether channel closure by tolbutamide reproduces the electrophysiological effects of glucose stimulation. We recorded membrane electrical activity from freshly dissected adult mouse pancreatic islets exposed to various levels of glucose and tolbutamide. As previously found by others, tolbutamide depolarizes islet cells in the absence of glucose, but we have found that, although the depolarization can trigger Ca2+ action potentials (spikes), a glucose-dependent permissive factor may be required for the normal bursting pattern of spiking. More significantly, we found that, unlike other β-cell stimuli, tolbutamide specifically mimics the effects of glucose stimulation on the pattern of suprathreshold electrical activity. The effects were seen with levels of tolbutamide that correspond to those required to inhibit ATP-sensitive K+ channels. These data suggest that ATP-sensitive K+ channels are active at sub- and suprathreshold levels of glucose and may be the sole pathway by which either glucose or tolbutamide depolarizes β-cells and controls β-cell electrical activity.
Tolbutamide as Mimic of Glucose on β-Cell Electrical Activity: ATP-Sensitive K+ Channels as Common Pathway for Both Stimuli
- Views Icon Views
- Share Icon Share
Daniel L Cook, Masatoshi Ikeuchi; Tolbutamide as Mimic of Glucose on β-Cell Electrical Activity: ATP-Sensitive K+ Channels as Common Pathway for Both Stimuli. Diabetes 1 April 1989; 38 (4): 416–421. https://doi.org/10.2337/diab.38.4.416
Download citation file: