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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

Western blotting in human pancreas islet β cells after 24 hours of different concentrations of four statin treatments.Notes: (A and B) GLUT-2, (C and D) PKA, (E and F) p-p38 MAPK. *P<0.05 and **P<0.01 vs control group.Abbreviations: GLUT-2, glucose transporter 2; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.
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f6-dddt-9-6211: Western blotting in human pancreas islet β cells after 24 hours of different concentrations of four statin treatments.Notes: (A and B) GLUT-2, (C and D) PKA, (E and F) p-p38 MAPK. *P<0.05 and **P<0.01 vs control group.Abbreviations: GLUT-2, glucose transporter 2; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.

Mentions: As shown in Figure 6, atorvastatin and pravastatin elicited a concentration-dependent inhibition of GLUT-2 expression in human pancreas islet β cells, while rosuvastatin and pitavastatin showed a slight increase in GLUT-2 expression. However, the four statins showed a concentration-dependent increase in p38 MAPK phosphorylation with a maximum of sevenfold to13-fold increase over control values at a concentration of 100 nM statin. The expression of total p38 MAPK was approximately the same among the four statins-treated groups and the control group. There was no significant difference of PKA levels in statin-treated groups at all three concentrations compared to the control group.


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

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

Western blotting in human pancreas islet β cells after 24 hours of different concentrations of four statin treatments.Notes: (A and B) GLUT-2, (C and D) PKA, (E and F) p-p38 MAPK. *P<0.05 and **P<0.01 vs control group.Abbreviations: GLUT-2, glucose transporter 2; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.
© Copyright Policy
Related In: Results  -  Collection

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

f6-dddt-9-6211: Western blotting in human pancreas islet β cells after 24 hours of different concentrations of four statin treatments.Notes: (A and B) GLUT-2, (C and D) PKA, (E and F) p-p38 MAPK. *P<0.05 and **P<0.01 vs control group.Abbreviations: GLUT-2, glucose transporter 2; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.
Mentions: As shown in Figure 6, atorvastatin and pravastatin elicited a concentration-dependent inhibition of GLUT-2 expression in human pancreas islet β cells, while rosuvastatin and pitavastatin showed a slight increase in GLUT-2 expression. However, the four statins showed a concentration-dependent increase in p38 MAPK phosphorylation with a maximum of sevenfold to13-fold increase over control values at a concentration of 100 nM statin. The expression of total p38 MAPK was approximately the same among the four statins-treated groups and the control group. There was no significant difference of PKA levels in statin-treated groups at all three concentrations compared to the control group.

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