Different effects of statins on induction of diabetes mellitus: an experimental study.

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Zhao W, Zhao SP

Different effects of statins on induction of diabetes mellitus: an experimental study.

Drug Des Devel Ther. 2015 Nov 24;9:6211-23. doi: 10.2147/DDDT.S87979. eCollection 2015.

PubMed ID
26648697 [ View in PubMed
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Abstract

BACKGROUND: To determine the effect of different statins on the induction of diabetes mellitus. MATERIALS AND 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 beta cells, and glucose uptake and signaling were studied in human skeletal muscle cells (HSkMCs). RESULTS: Human pancreas islet beta 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 beta cells. Atorvastatin, pravastatin, and rosuvastatin inhibited GLUT-4, p-AKT, p-GSK-3beta, and p-p38 MAPK levels in HSkMCs. CONCLUSION: Statins similar but different degree of effects on pancreas islet beta cells damage and induce insulin resistance in HSkMC.

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