Increased ATP-sensitive K + channel expression during acute glucose deprivation

Abstract

ATP-sensitive potassium (K ATP) channels play a central role in glucose-stimulated insulin secretion (GSIS) by pancreatic β-cells. Activity of these channels is determined by their open probability ( P o) and the number of channels present in a cell. Glucose is known to reduce P o, but whether it also affects the channel density is unknown. Using INS-1 model β-cell line, we show that the expression of K ATP channel subunits, Kir6.2 and SUR1, is high at low glucose, but declines sharply when the ambient glucose concentration exceeds 5 mM. In response to glucose deprivation, channel synthesis increases rapidly by up-regulating translation of existing mRNAs. The effects of glucose deprivation could be mimicked by pharmacological activation of 5′-AMP-activated protein kinase with 5-aminoimidazole-4-carboxamide ribonucleotide and metformin. Pancreatic β-cells which have lost their ability for GSIS do not show such changes implicating a possible (patho-)physiological link between glucose-regulated K ATP channel expression and the capacity for normal GSIS.