Referenced in: none

Automatically associated channels: Kir6.2

Title: Defective insulin secretion and enhanced insulin action in KATP channel-deficient mice.

Authors: T Miki, K Nagashima, F Tashiro, K Kotake, H Yoshitomi, A Tamamoto, T Gonoi, T Iwanaga, J Miyazaki, S Seino

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 1998 Sep 1 , 95, 10402-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9724715

Abstract
ATP-sensitive K+ (KATP) channels regulate many cellular functions by linking cell metabolism to membrane potential. We have generated KATP channel-deficient mice by genetic disruption of Kir6.2, which forms the K+ ion-selective pore of the channel. The homozygous mice (Kir6.2(-/-)) lack KATP channel activity. Although the resting membrane potential and basal intracellular calcium concentrations ([Ca2+]i) of pancreatic beta cells in Kir6.2(-/-) are significantly higher than those in control mice (Kir6.2(+/+)), neither glucose at high concentrations nor the sulfonylurea tolbutamide elicits a rise in [Ca2+]i, and no significant insulin secretion in response to either glucose or tolbutamide is found in Kir6.2(-/-), as assessed by perifusion and batch incubation of pancreatic islets. Despite the defect in glucose-induced insulin secretion, Kir6.2(-/-) show only mild impairment in glucose tolerance. The glucose-lowering effect of insulin, as assessed by an insulin tolerance test, is increased significantly in Kir6.2(-/-), which could protect Kir6.2(-/-) from developing hyperglycemia. Our data indicate that the KATP channel in pancreatic beta cells is a key regulator of both glucose- and sulfonylurea-induced insulin secretion and suggest also that the KATP channel in skeletal muscle might be involved in insulin action.