Abstract
β cells rely on adenosine triphosphate-sensitive potassium (KATP) channels to initiate and end glucose-stimulated insulin secretion through changes in membrane potential. These channels may also act as a constituent of the exocytotic machinery to mediate insulin release independent of their electrical function. However, the molecular mechanisms whereby the β cell plasma membrane maintains an appropriate number of KATP channels are not known. We now show that glucose increases KATP current amplitude by increasing the number of KATP channels in the β cell plasma membrane. The effect was blocked by inhibition of protein kinase A (PKA) as well as by depletion of extracellular or intracellular Ca2+. Furthermore, glucose promoted recruitment of the potassium inward rectifier 6.2 to the plasma membrane, and intracellular KATP channels localized in chromogranin-positive/insulin-negative dense-core granules. Our data suggest that glucose can recruit KATP channels to the β cell plasma membrane via non-insulin-containing dense-core granules in a Ca2+- and PKA-dependent manner.
