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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

The relative cell viability (%) after 24 hours of different concentrations of four statin treatments.Notes: *P<0.05 and ***P<0.001 vs control group. ^P<0.05 and ^^P<0.01 between indicated groups.
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f1-dddt-9-6211: The relative cell viability (%) after 24 hours of different concentrations of four statin treatments.Notes: *P<0.05 and ***P<0.001 vs control group. ^P<0.05 and ^^P<0.01 between indicated groups.

Mentions: We first examined the cytotoxic effects of statins on human pancreas islet β cells using the MTT reduction assay. Statins decreased cell viability of human pancreas islet β cells in a dose-dependent manner (Figure 1). Cells treated with 100 nM atorvastatin, pravastatin, rosuvastatin, and pitavastatin for 24 hours had reduced cell viability (32.12%, 41.09%, 33.96%, and 29.19% reduction, all P<0.001 vs controls) relative to control cells, respectively. This cytotoxic effect was significantly attenuated by decreasing the dose to 10 and 1 nM (reduction rate ranged from 1.46% to 17.28%, all P<0.05 for 10 nM and P>0.05 for 1 nM vs controls), suggesting that statin-induced cytotoxic effect was dose-dependent (Figure 1).


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

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

The relative cell viability (%) after 24 hours of different concentrations of four statin treatments.Notes: *P<0.05 and ***P<0.001 vs control group. ^P<0.05 and ^^P<0.01 between indicated groups.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4664500&req=5

f1-dddt-9-6211: The relative cell viability (%) after 24 hours of different concentrations of four statin treatments.Notes: *P<0.05 and ***P<0.001 vs control group. ^P<0.05 and ^^P<0.01 between indicated groups.
Mentions: We first examined the cytotoxic effects of statins on human pancreas islet β cells using the MTT reduction assay. Statins decreased cell viability of human pancreas islet β cells in a dose-dependent manner (Figure 1). Cells treated with 100 nM atorvastatin, pravastatin, rosuvastatin, and pitavastatin for 24 hours had reduced cell viability (32.12%, 41.09%, 33.96%, and 29.19% reduction, all P<0.001 vs controls) relative to control cells, respectively. This cytotoxic effect was significantly attenuated by decreasing the dose to 10 and 1 nM (reduction rate ranged from 1.46% to 17.28%, all P<0.05 for 10 nM and P>0.05 for 1 nM vs controls), suggesting that statin-induced cytotoxic effect was dose-dependent (Figure 1).

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