| http://purl.uniprot.org/citations/16924481 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16924481 | http://www.w3.org/2000/01/rdf-schema#comment | "Aims/hypothesisATP-sensitive K(+) (K(ATP)) channels couple glucose metabolism to insulin secretion in pancreatic beta cells. In humans, loss-of-function mutations of beta cell K(ATP) subunits (SUR1, encoded by the gene ABCC8, or Kir6.2, encoded by the gene KCNJ11) cause congenital hyperinsulinaemia. Mice with dominant-negative reduction of beta cell K(ATP) (Kir6.2[AAA]) exhibit hyperinsulinism, whereas mice with zero K(ATP) (Kir6.2(-/-)) show transient hyperinsulinaemia as neonates, but are glucose-intolerant as adults. Thus, we propose that partial loss of beta cell K(ATP) in vivo causes insulin hypersecretion, but complete absence may cause insulin secretory failure.Materials and methodsHeterozygous Kir6.2(+/-) and SUR1(+/-) animals were generated by backcrossing from knockout animals. Glucose tolerance in intact animals was determined following i.p. loading. Glucose-stimulated insulin secretion (GSIS), islet K(ATP) conductance and glucose dependence of intracellular Ca(2+) were assessed in isolated islets.ResultsIn both of the mechanistically distinct models of reduced K(ATP) (Kir6.2(+/-) and SUR1(+/-)), K(ATP) density is reduced by approximately 60%. While both Kir6.2(-/-) and SUR1(-/-) mice are glucose-intolerant and have reduced glucose-stimulated insulin secretion, heterozygous Kir6.2(+/-) and SUR1(+/-) mice show enhanced glucose tolerance and increased GSIS, paralleled by a left-shift in glucose dependence of intracellular Ca(2+) oscillations.Conclusions/interpretationThe results confirm that incomplete loss of beta cell K(ATP) in vivo underlies a hyperinsulinaemic phenotype, whereas complete loss of K(ATP) underlies eventual secretory failure."xsd:string |
| http://purl.uniprot.org/citations/16924481 | http://purl.org/dc/terms/identifier | "doi:10.1007/s00125-006-0367-4"xsd:string |
| http://purl.uniprot.org/citations/16924481 | http://purl.uniprot.org/core/author | "Nichols C.G."xsd:string |
| http://purl.uniprot.org/citations/16924481 | http://purl.uniprot.org/core/author | "Remedi M.S."xsd:string |
| http://purl.uniprot.org/citations/16924481 | http://purl.uniprot.org/core/author | "Tong A."xsd:string |
| http://purl.uniprot.org/citations/16924481 | http://purl.uniprot.org/core/author | "Piston D.W."xsd:string |
| http://purl.uniprot.org/citations/16924481 | http://purl.uniprot.org/core/author | "Rocheleau J.V."xsd:string |
| http://purl.uniprot.org/citations/16924481 | http://purl.uniprot.org/core/author | "Patton B.L."xsd:string |
| http://purl.uniprot.org/citations/16924481 | http://purl.uniprot.org/core/author | "Koster J.C."xsd:string |
| http://purl.uniprot.org/citations/16924481 | http://purl.uniprot.org/core/author | "McDaniel M.L."xsd:string |
| http://purl.uniprot.org/citations/16924481 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16924481 | http://purl.uniprot.org/core/name | "Diabetologia"xsd:string |
| http://purl.uniprot.org/citations/16924481 | http://purl.uniprot.org/core/pages | "2368-2378"xsd:string |
| http://purl.uniprot.org/citations/16924481 | http://purl.uniprot.org/core/title | "Hyperinsulinism in mice with heterozygous loss of K(ATP) channels."xsd:string |
| http://purl.uniprot.org/citations/16924481 | http://purl.uniprot.org/core/volume | "49"xsd:string |
| http://purl.uniprot.org/citations/16924481 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16924481 |
| http://purl.uniprot.org/citations/16924481 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/16924481 |
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