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

Zhao W, Zhao SP - Drug Des Devel Ther (2015)

Bottom Line: 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.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.Statins similar but different degree of effects on pancreas islet β cells damage and induce insulin resistance in HSkMC.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

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 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.

Conclusion: Statins similar but different degree of effects on pancreas islet β cells damage and induce insulin resistance in HSkMC.

No MeSH data available.


Related in: MedlinePlus

DNA histograms after 24 hours of different concentrations of four statin treatments.Notes: (A–C) Atorvastatin (1, 10, and 100 µM, respectively), (D–F) pravastatin (1, 10, and 100 µM, respectively), (G–I) rosuvastatin (1, 10, and 100 µM, respectively), (J–L) pitavastatin (1, 10, and 100 µM, respectively), and (M) control.
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f3-dddt-9-6211: DNA histograms after 24 hours of different concentrations of four statin treatments.Notes: (A–C) Atorvastatin (1, 10, and 100 µM, respectively), (D–F) pravastatin (1, 10, and 100 µM, respectively), (G–I) rosuvastatin (1, 10, and 100 µM, respectively), (J–L) pitavastatin (1, 10, and 100 µM, respectively), and (M) control.

Mentions: Statin-induced G0/G1 phase cell cycle arrest in human pancreas islet β cells also showed a dose-dependent pattern. The four statins induced G0/G1 cell cycle arrest at a low concentration (1 nM), where the G0/G1 DNA content was higher in statin-treated cells compared with control treatment in both cell lines. At a moderate concentration (10 nM), the G0/G1 DNA content of the four statin-treated groups was approximately the same as the low concentration (1 nM). At a high concentration (100 nM), the G0/G1 DNA content of the four drug-treatment groups was much higher than the low and moderate concentration groups, rising to 80.36%–86.28%. The proliferation of human pancreas islet β cells was significantly inhibited by statins at a high concentration (Figures 3 and 4).


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

Zhao W, Zhao SP - Drug Des Devel Ther (2015)

DNA histograms after 24 hours of different concentrations of four statin treatments.Notes: (A–C) Atorvastatin (1, 10, and 100 µM, respectively), (D–F) pravastatin (1, 10, and 100 µM, respectively), (G–I) rosuvastatin (1, 10, and 100 µM, respectively), (J–L) pitavastatin (1, 10, and 100 µM, respectively), and (M) control.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664500&req=5

f3-dddt-9-6211: DNA histograms after 24 hours of different concentrations of four statin treatments.Notes: (A–C) Atorvastatin (1, 10, and 100 µM, respectively), (D–F) pravastatin (1, 10, and 100 µM, respectively), (G–I) rosuvastatin (1, 10, and 100 µM, respectively), (J–L) pitavastatin (1, 10, and 100 µM, respectively), and (M) control.
Mentions: Statin-induced G0/G1 phase cell cycle arrest in human pancreas islet β cells also showed a dose-dependent pattern. The four statins induced G0/G1 cell cycle arrest at a low concentration (1 nM), where the G0/G1 DNA content was higher in statin-treated cells compared with control treatment in both cell lines. At a moderate concentration (10 nM), the G0/G1 DNA content of the four statin-treated groups was approximately the same as the low concentration (1 nM). At a high concentration (100 nM), the G0/G1 DNA content of the four drug-treatment groups was much higher than the low and moderate concentration groups, rising to 80.36%–86.28%. The proliferation of human pancreas islet β cells was significantly inhibited by statins at a high concentration (Figures 3 and 4).

Bottom Line: 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.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.Statins similar but different degree of effects on pancreas islet β cells damage and induce insulin resistance in HSkMC.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

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 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.

Conclusion: Statins similar but different degree of effects on pancreas islet β cells damage and induce insulin resistance in HSkMC.

No MeSH data available.


Related in: MedlinePlus