title: Differential impact of atorvastatin vs pravastatin on progressive insulin resistance and left ventricular diastolic dysfunction in a rat model of type II diabetes.
abstract: BACKGROUND
  Controversy exists regarding the effects of statin therapy on progressive insulin resistance (IR) and its consequences, in the present study a rat model of spontaneously developing type II diabetes mellitus (DM) was used to examine the impact of atorvastatin (AS) vs pravastatin (PS).
  
  
  RESULTS
  The Otsuka Long-Evans Tokushima Fatty rats were either untreated or treated with 100 mg/kg per day of AS or PS from 6 weeks of age for 24 weeks. AS achieved much greater lipid lowering than PS. Serial oral glucose tolerance tests revealed new-onset diabetes was delayed by PS only. The untreated rats exhibited a progressive decrease in plasma adiponectin, increases in plasma leptin and tumor necrosis factor-alpha, and reduction of plasma nitric oxide (NO), which were limited more by PS than AS. PS, but not AS, enhanced adiponectin mRNA expression in white adipose tissue at 30 weeks. Cardiac endothelial NO synthase expression was upregulated, and overexpression of both transforming growth factor-beta1 and monocyte chemoattractant protein-1 mRNA was limited more by PS than AS. Coronary perivascular fibrosis at 30 weeks was suppressed only by PS, which was accompanied by preserved left ventricular diastolic function assessed with Doppler echocardiography.
  
  
  CONCLUSIONS
  The moderate lipid lowering by PS, but not the intensive lipid lowering by AS, prevented new-onset DM and diastolic dysfunction in a rat model of IR, and this was associated with preferable adipocytokine profiles and cardiac redox states.
authors.affiliation: Department of Cardiorenal Cerebrovascular Medicine, Kagawa University School of Medicine, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Koji
authors.initials: K
authors.lastname: Ohmori
authors.forename: Mizuki
authors.initials: M
authors.lastname: Mizukawa
authors.forename: Junji
authors.initials: J
authors.lastname: Yoshida
authors.forename: Yu
authors.initials: Y
authors.lastname: Zeng
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Kaori
authors.initials: K
authors.lastname: Shinomiya
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kosaka
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D015228:Hypertriglyceridemia / Q000188:drug therapy / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000097:blood; D009206:Myocardium / Q000201:enzymology; D009569:Nitric Oxide / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011922:Rats, Mutant Strains; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D052242:Adiponectin; D000924:Anticholesteremic Agents; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D006538:Heptanoic Acids; D020738:Leptin; D011758:Pyrroles; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; D000069059:Atorvastatin; D052250:Nitric Oxide Synthase Type III; D005947:Glucose; D017035:Pravastatin