title: Reduced cardiotropic response to insulin in spontaneously hypertensive rats: role of peroxisome proliferator-activated receptor-gamma-initiated signaling.
abstract: OBJECTIVE
  Vascular insulin resistance plays a crucial pathogenic role in the development of genetic hypertension. However, it is not known whether hypertension-associated myocardial insulin resistance also exists, and whether this is involved in the development of related diseases, such as hypertensive heart failure. The present study aimed to determine whether hypertension-associated myocardial insulin resistance exists, in addition to any underlying mechanism.
  
  
  METHODS
  Ventricular myocytes were enzymatically isolated from male Wistar-Kyoto (WKY) rats or spontaneously hypertensive rats (SHR) and myocyte shortening and intracellular Ca2+ transient were assessed, as was any signaling mechanism.
  
  
  RESULTS
  Compared with WKY rats, insulin-stimulated myocardial glucose uptake was blunted in SHR. More importantly, the positive inotropic effect of insulin was significantly reduced in SHR myocytes. Moreover, peroxisome proliferator-activated receptor (PPAR)gamma and phosphatidylinositol 3 (PI-3) kinase p85 expression and insulin-induced Akt phosphorylation were reduced in SHR cardiomyocytes, but were markedly restored when animals were treated with rosiglitazone for 14 days. Pretreatment with an Akt inhibitor abolished the inotropic effect induced by insulin in rosiglitazone-treated SHR cardiomyocytes.
  
  
  CONCLUSIONS
  The data obtained demonstrate that insulin resistance exists in SHR cardiomyocytes as manifested by both reduced insulin-stimulated glucose uptake and an impaired contractile response to insulin, which is attributable to decreased PPARgamma expression and subsequent impairment in PI-3 kinase/Akt signaling.
authors.affiliation: Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Quanjiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Heng
authors.initials: H
authors.lastname: Ma
authors.forename: Qiuhe
authors.initials: Q
authors.lastname: Ji
authors.forename: Wenyi
authors.initials: W
authors.lastname: Guo
authors.forename: Haichang
authors.initials: H
authors.lastname: Wang
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Lopez
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Christopher
authors.forename: Xinliang
authors.initials: X
authors.lastname: Ma
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression; D006973:Hypertension / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; D045162:Thiazolidinediones; D014665:Vasodilator Agents; D000077154:Rosiglitazone; D019869:Phosphatidylinositol 3-Kinases