title: Enhanced hepatic insulin signaling in the livers of high altitude native rats under basal conditions and in the livers of low altitude native rats under insulin stimulation: a mechanistic study.
abstract: This study was designed to investigate the role of the liver in lowering fasting blood glucose levels (FBG) in rats native to high (HA) and low altitude (LA) areas. As compared with LA natives, besides the improved insulin and glucose tolerance, HA native rats had lower FBG, at least mediated by inhibition of hepatic gluconeogenesis and activation of glycogen synthesis. An effect that is mediated by the enhancement of hepatic insulin signaling mediated by the decreased phosphorylation of TSC induced inhibition of mTOR function. Such effect was independent of activation of AMPK nor stabilization of HIF1α, but most probably due to oxidative stress induced REDD1 expression. However, under insulin stimulation, and in spite of the less activated mTOR function in HA native rats, LA native rats had higher glycogen content and reduced levels of gluconeogenic enzymes with a more enhanced insulin signaling, mainly due to higher levels of p-IRS1 (tyr612).
authors.affiliation: a Department of Basic Medical Sciences , Divison of Physiology, College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) , Riyadh , Saudi Arabia.|b King Abdullah International Medical Research Center (KAIMRC) , Riyadh , Saudi Arabia.|c Rehabilitation Department, King Abdulaziz Medical City , Riyadh , Saudi Arabia.
authors.forename: Hussain
authors.initials: H
authors.lastname: Al Dera
authors.affiliation: d Department of Applied medical Sciences , College of Health Sciences, PAAET , Kuwait.
authors.forename: Samy M
authors.initials: SM
authors.lastname: Eleawa
authors.affiliation: e Department of Physiology , College of Medicine, King Khalid University , Abha , Saudi Arabia.
authors.forename: Fahaid H
authors.initials: FH
authors.lastname: Al-Hashem
authors.affiliation: f Department of Medical Education , College of Medicine, King's Saud bin Abdulaziz University for Health Sciences , Riyadh , Saudi Arabia , and.|g Divison of Endocrinology, Department of Medicine, King's Abdulaziz Medical City , Riyadh , Saudi Arabia.
authors.forename: Moeber M
authors.initials: MM
authors.lastname: Mahzari
authors.affiliation: a Department of Basic Medical Sciences , Divison of Physiology, College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) , Riyadh , Saudi Arabia.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Hoja
authors.affiliation: a Department of Basic Medical Sciences , Divison of Physiology, College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) , Riyadh , Saudi Arabia.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Al Khateeb
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000531:Altitude; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005215:Fasting; D005786:Gene Expression Regulation; D005943:Gluconeogenesis / Q000235:genetics; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000096:biosynthesis; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D001786:Blood Glucose; D002135:Calcium-Binding Proteins; C000632146:Ddit4 protein, rat; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D012097:Repressor Proteins; C000606248:Tesc protein, rat; D014157:Transcription Factors; D006003:Glycogen; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK; High altitude; insulin; liver; rats