title: Different effects of statins on induction of diabetes mellitus: an experimental study.
abstract: BACKGROUND
  To determine the effect of different statins on the induction of diabetes mellitus.
  
  
  METHODS
  Four statins (atorvastatin, pravastatin, rosuvastatin, and pitavastatin) were used. Cytotoxicity, insulin secretion, glucose-stimulated insulin secretion, and G0/G1 phase cell cycle arrest were investigated in human pancreas islet β cells, and glucose uptake and signaling were studied in human skeletal muscle cells (HSkMCs).
  
  
  RESULTS
  Human pancreas islet β cells treated with 100 nM atorvastatin, pravastatin, rosuvastatin, and pitavastatin had reduced cell viability (32.12%, 41.09%, 33.96%, and 29.19%, respectively) compared to controls. Such cytotoxic effect was significantly attenuated by decreasing the dose to 10 and 1 nM, ranged from 1.46% to 17.28%. Cells treated with 100 nM atorvastatin, pravastatin, rosuvastatin, and pitavastatin had a reduction in the rate of insulin secretion rate by 34.07%, 30.06%, 26.78%, and 19.22%, respectively. The inhibitory effect was slightly attenuated by decreasing the dose to 10 and 1 nM, ranging from 10.84% to 29.60%. Insulin secretion stimulated by a high concentration of glucose (28 mmol/L) was significantly higher than a physiologic concentration of glucose (5.6 mmol/L) in all treatment groups. The glucose uptake rates at a concentration of 100 nM were as follows: atorvastatin (58.76%) < pravastatin (60.21%) < rosuvastatin (72.54%) < pitavastatin (89.96%). We also found that atorvastatin and pravastatin decreased glucose transporter (GLUT)-2 expression and induced p-p38 MAPK levels in human pancreas islet β cells. Atorvastatin, pravastatin, and rosuvastatin inhibited GLUT-4, p-AKT, p-GSK-3β, and p-p38 MAPK levels in HSkMCs.
  
  
  CONCLUSIONS
  Statins similar but different degree of effects on pancreas islet β cells damage and induce insulin resistance in HSkMC.
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Wang
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Shui-Ping
authors.initials: SP
authors.lastname: Zhao
mesh_terms: D000069059:Atorvastatin / Q000009:adverse effects / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000139:chemically induced* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects; D017035:Pravastatin / Q000008:administration & dosage / Q000633:toxicity*; D011804:Quinolines / Q000008:administration & dosage / Q000633:toxicity*; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D007328:Insulin; D011804:Quinolines; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D005947:Glucose; D017035:Pravastatin; C108475:pitavastatin
keywords: glucose; human pancreas islet β cell; human skeletal muscle cells; insulin; statins