Linked Life Data

15855351

Source:http://linkedlifedata.com/resource/pubmed/id/15855351

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-4-27
pubmed:abstractText
ATP-sensitive K+ channels (K(ATP) channels) play an important role in glucose homeostasis. A single nucleotide polymorphism (SNP) in the Kir6.2 subunit causes a point mutation of Glu23 to lysine and reduces the ATP sensitivity of pancreatic K(ATP) channels. The SNP found in 58% of Caucasians accounts for 15% of type 2 diabetes. Here we show evidence for dysregulations of muscular K(ATP) channels with the E23K variation. We were particularly interested in the channel modulation by intracellular protons, as pH changes widely and frequently in skeletal muscles. Surprisingly, we found that the defect of the E23K variant was more related to pH than ATP. A level of intracellular acidification seen during exercise not only activated the E23K channel more readily than the wild type, but also relieved the channel inhibition by ATP, leading to a vast increase in the channel open-state probability by approximately sevenfold at pH 6.8 over the wild-type channel at pH 7.4. Considering the reduction in sarcolemmal excitability, muscle fatigue, and impairment of muscular glucose uptake found previously by genetically disrupting K(ATP) channels, it is likely that the E23K variant in muscular K(ATP) channels affects systemic glucose homeostasis and poses an important risk factor for type 2 diabetes and obesity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1592-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Single nucleotide polymorphisms in K(ATP) channels: muscular impact on type 2 diabetes.
pubmed:affiliation
Department of Biology, Georgia State University, 24 Peachtree Center Ave., Atlanta, Georgia 30302-4010, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural