抄録
Electrically-excitable cells of which firing rate is increased in response to glucose are called glucose-responsive (GR) cells. They are present in several tissues such as endocrine pancreas, gut and brain. In pancreatic β-cells, ATP-sensitive K+ (KATP) channels are essential for the regulation of cellular excitability by glucose and glucose-induced insulin secretion. In gut, KATP channels are detected in GR cholinergic neurons and are suggested to be involved in the glucose-induced membrane depolarization of these peripheral neurons. In central nervous system, GR neurons exist at the highest density in the ventromedial hypothalamus (VMH), the region important in sensing ambient glucose levels. KATP channels in the VMH are identical to that of pancreatic β-cells, which is composed of Kir6.2 and SUR1. Analysis of the mice lacking Kir6.2 (Kir6.2−/− mice) have clarified that the channels are essential for regulating the firing rate of GR neurons in response to glucose. Thus, GR neurons of the VMH and pancreatic β-cell not only possess the same KATP channels but also are equipped with similar glucose-sensing apparatus. Kir6.2−/− mice exhibit an impaired glucagon secretion in response to hypoglycemia and attenuated feeding response to neuronal glycopenia induced by 2-deoxyglucose. KATP channels in the skeletal muscles are also involved in the glucose uptake. Thus, the KATP channels, as central and peripheral glucose sensors, are critical in the maintenance of glucose homeostasis. [Jpn J Physiol 55 Suppl:S58 (2005)]
