title: Anti-diabetes effect of chronic intermittent hypobaric hypoxia through improving liver insulin resistance in diabetic rats.
abstract: OBJECTIVE
  Cumulating evidence demonstrated that chronic intermittent hypobaric hypoxia (CIHH) had beneficial effects on the body. The present study was to investigate the anti-diabetes effect of CIHH in type-2 diabetic rats for the first time.
  
  
  METHODS
  Sprague-Dawley rats were randomly divided into 4 groups: control group (CON), diabetes mellitus group (DM, induced by high-fat diet combined with low-dose streptozotocin), CIHH treatment group (CIHH, simulated 5000-m altitude, 6h per day for 28 days), and diabetes mellitus plus CIHH treatment group (DM+CIHH). Histopathology of liver, systolic arterial blood pressure (SAP), blood biochemicals, glucose and insulin tolerance were determined. The expression of proteins associated with insulin signaling pathway as well as hypoxia induced factors were assayed.
  
  
  RESULTS
  Diabetic rats showed impaired glucose tolerance, dyslipidemia, hepatic steatosis and hepatic insulin resistance in addition to increased SAP. However, SAP, serum triglyceride and cholesterol were decreased, and hepatic steatosis and insulin resistance were improved in DM+CIHH rats. Furthermore, the protein expression of glucokinase (GCK), insulin receptor substrates (IRS-1 and IRS-2), and HIF1α were increased, while the expression of phosphoenolpyruvate carboxykinase (PEPCK), was markedly reduced in DM+CIHH rats.
  
  
  CONCLUSIONS
  We conclude that CIHH treatment has anti-diabetes effects through ameliorating insulin resistance via hepatic HIF-insulin signaling pathway in type-2 diabetic rats.
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang 050000, PR China.
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Tian
authors.affiliation: Department of Endocrinology, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang 050000, PR China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Tong
authors.initials: T
authors.lastname: Su
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang 050000, PR China. Electronic address: lily564300@163.com.
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Ma
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang 050000, PR China. Electronic address: zhyhenryphy@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000399:Air Pressure; D000818:Animals; D062186:Arterial Pressure; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000628:therapy*; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D059305:Diet, High-Fat; D050171:Dyslipidemias / Q000209:etiology / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism; D005951:Glucose Tolerance Test; D000860:Hypoxia; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008099:Liver / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008055:Lipids
keywords: CIHH; HIF; IRS; Insulin resistance; Type 2 diabetes mellitus