title: Swim training sensitizes myocardial response to insulin: role of Akt-dependent eNOS activation.
abstract: OBJECTIVE
  Physical activity has been well known to benefit heart function. The improved autonomic nervous activity is considered to be mainly responsible for this beneficial effect. However, the precise mechanism behind the intrinsic myocardial responsiveness to exercise is still unclear. This study was designed to examine the effect of swim training on myocardial response to insulin with a special focus on the endogenous endothelial nitric oxide synthase (eNOS)-nitric oxide (NO) cascade.
  
  
  METHODS
  Adult male Sprague-Dawley (SD) rats were subjected to a 10-week free-loading swim training (3 h/day, 5 days/week). Contractile response to insulin at the levels of cardiomyocytes and isolated perfused heart, myocardial glucose uptake and post-insulin receptor signaling cascades were evaluated.
  
  
  RESULTS
  Swim training enhanced cardiac contractile response to insulin in cardiomyocytes and isolated perfused heart, respectively. The improved cardiac response was accompanied by facilitated insulin-stimulated glucose uptake, GLUT4 translocation and upregulation of Akt and eNOS expression (p<0.01). Treatment with insulin resulted in a 3.6- and 2.2-fold increase of eNOS phosphorylation (p<0.01), as well as a 3.0- and 1.9-fold increase of Akt phosphorylation in exercise and sedentary groups, respectively (p<0.01). In addition, exercise significantly facilitated insulin-induced myocardial NO production (p<0.01 vs. sedentary). Moreover, pretreatment with either LY294002, a phosphatidylinositol-3 kinase (PI-3K) inhibitor or L-NAME, a NOS inhibitor, abolished the exercise-induced sensitization of myocardial contractile response to insulin, insulin-induced NO production and phosphorylation of Akt and eNOS.
  
  
  CONCLUSIONS
  These results demonstrate that swim training is capable of sensitizing myocardial contractile response to insulin via upregulation of Akt- and eNOS signaling cascades.
authors.affiliation: Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032, China.
authors.forename: Quan-Jiang
authors.initials: QJ
authors.lastname: Zhang
authors.forename: Qiu-Xia
authors.initials: QX
authors.lastname: Li
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Zhang
authors.forename: Kun-Ru
authors.initials: KR
authors.lastname: Zhang
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Guo
authors.forename: Hai-Chang
authors.initials: HC
authors.lastname: Wang
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Zhou
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Cheng
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000818:Animals; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009200:Myocardial Contraction; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010477:Perfusion; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D010807:Physical Endurance; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming; D015854:Up-Regulation
chemical_list: D002867:Chromones; D051275:Glucose Transporter Type 4; D007328:Insulin; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester