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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 insulin secretion stimulation index high glucose stimulation/physiologic glucose stimulation ratio after 24 hours of different concentrations of four statin treatments.Notes: *P<0.05 and **P<0.01 vs control group.
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f2-dddt-9-6211: The insulin secretion stimulation index high glucose stimulation/physiologic glucose stimulation ratio after 24 hours of different concentrations of four statin treatments.Notes: *P<0.05 and **P<0.01 vs control group.

Mentions: The insulin secretion stimulated by a high glucose concentration (28 mmol/L) was significantly higher than a physiologic concentration (5.6 mmol/L) in all statin treatment groups, ranging from 53.44 to 78.32 ng/mL and from 35.78 to 54.22 ng/mL, respectively (data not shown). Upon physiologic glucose level (5.6 mmol/L) stimulation, the insulin secretion by pancreas islet β cells was the highest in pitavastatin group (range 46.29–51.05 ng/mL) and the lowest in pravastatin group (range 35.77–40.99 ng/mL) at the three concentration levels (data not shown in figure). The findings were similar under high glucose concentration (28 mmol/L) stimulation condition, ranging from 71.94 to 78.32 ng/mL in the pitavastatin group and from 53.44 to 65.86 ng/mL in pravastatin group at the three concentration levels (data not shown in figure). Therefore, we obtained a similar finding in a further analysis using the high glucose stimulation/low glucose stimulation index. The glucose stimulation index significantly decreased between control and 100 nM statin treatment of all four statins (Figure 2). Besides, pravastatin showed a significant decreased glucose stimulation index even at a relatively low concentration (10 nM; Figure 2).


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

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

The insulin secretion stimulation index high glucose stimulation/physiologic glucose stimulation ratio after 24 hours of different concentrations of four statin treatments.Notes: *P<0.05 and **P<0.01 vs control group.
© Copyright Policy
Related In: Results  -  Collection

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

f2-dddt-9-6211: The insulin secretion stimulation index high glucose stimulation/physiologic glucose stimulation ratio after 24 hours of different concentrations of four statin treatments.Notes: *P<0.05 and **P<0.01 vs control group.
Mentions: The insulin secretion stimulated by a high glucose concentration (28 mmol/L) was significantly higher than a physiologic concentration (5.6 mmol/L) in all statin treatment groups, ranging from 53.44 to 78.32 ng/mL and from 35.78 to 54.22 ng/mL, respectively (data not shown). Upon physiologic glucose level (5.6 mmol/L) stimulation, the insulin secretion by pancreas islet β cells was the highest in pitavastatin group (range 46.29–51.05 ng/mL) and the lowest in pravastatin group (range 35.77–40.99 ng/mL) at the three concentration levels (data not shown in figure). The findings were similar under high glucose concentration (28 mmol/L) stimulation condition, ranging from 71.94 to 78.32 ng/mL in the pitavastatin group and from 53.44 to 65.86 ng/mL in pravastatin group at the three concentration levels (data not shown in figure). Therefore, we obtained a similar finding in a further analysis using the high glucose stimulation/low glucose stimulation index. The glucose stimulation index significantly decreased between control and 100 nM statin treatment of all four statins (Figure 2). Besides, pravastatin showed a significant decreased glucose stimulation index even at a relatively low concentration (10 nM; Figure 2).

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