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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

Altered human pancreas islet β cells and HSkMCs phenotype normalized after MAPK and AKT inhibitor treatment.Notes: (A) Human pancreas islet β cells survival, (B) insulin secretion stimulation index high glucose stimulation/physiologic glucose stimulation ratio of human pancreas islet β cells, (C) HSkMCs glucose uptake, and (D) p-AKT and p-p38 MAP signaling of HSkMCs. **P<0.01 and ***P<0.001 vs control group.Abbreviations: HSkMC, human skeletal muscle cell; OD, optical density; ns, not significant.
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f8-dddt-9-6211: Altered human pancreas islet β cells and HSkMCs phenotype normalized after MAPK and AKT inhibitor treatment.Notes: (A) Human pancreas islet β cells survival, (B) insulin secretion stimulation index high glucose stimulation/physiologic glucose stimulation ratio of human pancreas islet β cells, (C) HSkMCs glucose uptake, and (D) p-AKT and p-p38 MAP signaling of HSkMCs. **P<0.01 and ***P<0.001 vs control group.Abbreviations: HSkMC, human skeletal muscle cell; OD, optical density; ns, not significant.

Mentions: To further mechanistically prove that the altered human pancreas islet β cells and HSkMCs phenotype were due to induced MAPK signaling and suppressed MAPK/AKT signaling pathways, respectively, we treated the two types of cells with MAPK and AKT inhibitors. Inhibiting MAPK signaling in human pancreas islet β cells pretreated with atorvastatin led to the normalized cell survival rate (Figure 8A), and so as the glucose secretion upon stimulation reflected by glucose stimulation index (Figure 8B). These data suggested a causational relation between the induced MAPK signaling and statin treatment in human pancreas islet β cells. On the other hand, treating HSkMCs with MAPK and AKT signaling inhibitors (SB203580 and MK2206, respectively) led to decreased glucose uptake of, which recapitulate the glucose uptake change in HSkMCs treated with statin (Figure 8C and D).


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

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

Altered human pancreas islet β cells and HSkMCs phenotype normalized after MAPK and AKT inhibitor treatment.Notes: (A) Human pancreas islet β cells survival, (B) insulin secretion stimulation index high glucose stimulation/physiologic glucose stimulation ratio of human pancreas islet β cells, (C) HSkMCs glucose uptake, and (D) p-AKT and p-p38 MAP signaling of HSkMCs. **P<0.01 and ***P<0.001 vs control group.Abbreviations: HSkMC, human skeletal muscle cell; OD, optical density; ns, not significant.
© Copyright Policy
Related In: Results  -  Collection

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

f8-dddt-9-6211: Altered human pancreas islet β cells and HSkMCs phenotype normalized after MAPK and AKT inhibitor treatment.Notes: (A) Human pancreas islet β cells survival, (B) insulin secretion stimulation index high glucose stimulation/physiologic glucose stimulation ratio of human pancreas islet β cells, (C) HSkMCs glucose uptake, and (D) p-AKT and p-p38 MAP signaling of HSkMCs. **P<0.01 and ***P<0.001 vs control group.Abbreviations: HSkMC, human skeletal muscle cell; OD, optical density; ns, not significant.
Mentions: To further mechanistically prove that the altered human pancreas islet β cells and HSkMCs phenotype were due to induced MAPK signaling and suppressed MAPK/AKT signaling pathways, respectively, we treated the two types of cells with MAPK and AKT inhibitors. Inhibiting MAPK signaling in human pancreas islet β cells pretreated with atorvastatin led to the normalized cell survival rate (Figure 8A), and so as the glucose secretion upon stimulation reflected by glucose stimulation index (Figure 8B). These data suggested a causational relation between the induced MAPK signaling and statin treatment in human pancreas islet β cells. On the other hand, treating HSkMCs with MAPK and AKT signaling inhibitors (SB203580 and MK2206, respectively) led to decreased glucose uptake of, which recapitulate the glucose uptake change in HSkMCs treated with statin (Figure 8C and D).

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