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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 rate insulin secretion (%) after 24 hours of different concentrations of four statin treatments.Notes: **P<0.01 and ***P<0.001 vs control group. ^P<0.05 and ^^P<0.01 between indicated groups.
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f9-dddt-9-6211: The relative rate insulin secretion (%) after 24 hours of different concentrations of four statin treatments.Notes: **P<0.01 and ***P<0.001 vs control group. ^P<0.05 and ^^P<0.01 between indicated groups.

Mentions: A randomized, single-blind, placebo-controlled parallel study showed that despite beneficial reductions in LDL-C and Apo B levels after a 2-month treatment of atorvastatin, atorvastatin resulted in significant increased fasting insulin and HbA1c levels, consistent with insulin resistance and increased ambient glycemia in hypercholesterolemic patients.23 In the present study, we found 100 nM atorvastatin, pravastatin, and rosuvastatin treatment caused more significant statin-induced cytotoxicity in human pancreas islet β cells and statin-reduced insulin secretion compared with pitavastatin (Figures 1 and 9). Statin treatment (all four statins) reduced GSIS under high glucose (28 mmol/L) and physiologic conditions (5.6 mmol/L), with a greater decrease under high glucose conditions. Inhibition of GSIS was greatest in the pravastatin treatment group and lowest in the pitavastatin treatment group under high glucose and physiologic conditions.


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

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

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

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

f9-dddt-9-6211: The relative rate insulin secretion (%) after 24 hours of different concentrations of four statin treatments.Notes: **P<0.01 and ***P<0.001 vs control group. ^P<0.05 and ^^P<0.01 between indicated groups.
Mentions: A randomized, single-blind, placebo-controlled parallel study showed that despite beneficial reductions in LDL-C and Apo B levels after a 2-month treatment of atorvastatin, atorvastatin resulted in significant increased fasting insulin and HbA1c levels, consistent with insulin resistance and increased ambient glycemia in hypercholesterolemic patients.23 In the present study, we found 100 nM atorvastatin, pravastatin, and rosuvastatin treatment caused more significant statin-induced cytotoxicity in human pancreas islet β cells and statin-reduced insulin secretion compared with pitavastatin (Figures 1 and 9). Statin treatment (all four statins) reduced GSIS under high glucose (28 mmol/L) and physiologic conditions (5.6 mmol/L), with a greater decrease under high glucose conditions. Inhibition of GSIS was greatest in the pravastatin treatment group and lowest in the pitavastatin treatment group under high glucose and physiologic conditions.

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