title: Increase of insulin sensitivity and reversal of age-dependent glucose intolerance with inhibition of ASIC3.
abstract: Glucose tolerance progressively declines with age in humans and is often accompanied by insulin resistance and a high prevalence of type 2 diabetes. Little is known about the mechanism underlying the age-related changes in glucose metabolism. Here we reported that acid-sensing ion channel 3 (ASIC3) is functionally expressed in adipose cells. ASIC3(-/-) mice were protected against age-dependent glucose intolerance with enhanced insulin sensitivity. Acute administration of ASIC3-selective blocker APETx2 improved the glucose control and increased the insulin sensitivity in older (25-27 weeks) ASIC3(+/+) mice. Moreover, the enhanced glucose control in aging ASIC3(-/-) mice was associated with high baseline levels of Akt phosphorylation and high copy number of mitochondrial DNA in adipose tissues. Taken together, our data suggest that ASIC3 signaling might be involved in the control of age-dependent glucose intolerance and insulin resistance.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Shyh-Jer
authors.initials: SJ
authors.lastname: Huang
authors.forename: Wei-Shiung
authors.initials: WS
authors.lastname: Yang
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Lin
authors.forename: Hung-Chin
authors.initials: HC
authors.lastname: Wang
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chen
mesh_terms: D062565:Acid Sensing Ion Channels; D000273:Adipose Tissue / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D003064:Cnidarian Venoms / Q000494:pharmacology; D018149:Glucose Intolerance / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D015222:Sodium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: C501880:APETx2 protein, Anthopleura elegantissima; C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels; D003064:Cnidarian Venoms; D015222:Sodium Channels