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Simvastatin may induce insulin resistance through a novel fatty acid mediated cholesterol independent mechanism.

Kain V, Kapadia B, Misra P, Saxena U - Sci Rep (2015)

Bottom Line: Statins are a class of oral drugs that are widely used for treatment of hypercholesterolemia.We explored the possible mechanism of statin induced insulin resistance using a well-established cell based model and simvastatin as a prototype statin.Our data show that simvastatin induces insulin resistance in a cholesterol biosynthesis inhibition independent fashion but does so by a fatty acid mediated effect on insulin signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.

ABSTRACT
Statins are a class of oral drugs that are widely used for treatment of hypercholesterolemia. Recent clinical data suggest that chronic use of these drugs increases the frequency of new onset diabetes. Studies to define the risks of statin-induced diabetes and its underlying mechanisms are clearly necessary. We explored the possible mechanism of statin induced insulin resistance using a well-established cell based model and simvastatin as a prototype statin. Our data show that simvastatin induces insulin resistance in a cholesterol biosynthesis inhibition independent fashion but does so by a fatty acid mediated effect on insulin signaling pathway. These data may help design strategies for prevention of statin induced insulin resistance and diabetes in patients with hypercholesterolemia.

No MeSH data available.


Related in: MedlinePlus

Simvastatin does not impair PPAR-γ mediated glucose uptake: Mean basal and insulin stimulated (5 min and 10 min) uptake of 2-NBDG by L6 myotubes treated with Simvastatin (1 μM) and/or Pioglitazone (10 μM) for different time points as indicated. DMSO (0.1%) treated cells served as internal control. Values are shown as mean±SD after normalizing with the corresponding protein content and expressed relative to basal of control cells which was set to 1; *p < 0.05, **p < 0.01, versus corresponding control cells , bp < 0.005 versus corresponding Simvastatin treated cells (two way ANOVA).
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f3: Simvastatin does not impair PPAR-γ mediated glucose uptake: Mean basal and insulin stimulated (5 min and 10 min) uptake of 2-NBDG by L6 myotubes treated with Simvastatin (1 μM) and/or Pioglitazone (10 μM) for different time points as indicated. DMSO (0.1%) treated cells served as internal control. Values are shown as mean±SD after normalizing with the corresponding protein content and expressed relative to basal of control cells which was set to 1; *p < 0.05, **p < 0.01, versus corresponding control cells , bp < 0.005 versus corresponding Simvastatin treated cells (two way ANOVA).

Mentions: Cells were treated either with simvastatin or pioglitazone alone or with a combination of the two drugs. Pioglitazone is a known PPAR gamma activator. As shown in Fig. 3, simvastatin alone had little effect on non-insulin stimulated glucose uptake. But combination of simvastatin with pioglitazone or pioglitazone alone showed substantial (~200% compared to DMSO treated control cells) increase in glucose uptake.


Simvastatin may induce insulin resistance through a novel fatty acid mediated cholesterol independent mechanism.

Kain V, Kapadia B, Misra P, Saxena U - Sci Rep (2015)

Simvastatin does not impair PPAR-γ mediated glucose uptake: Mean basal and insulin stimulated (5 min and 10 min) uptake of 2-NBDG by L6 myotubes treated with Simvastatin (1 μM) and/or Pioglitazone (10 μM) for different time points as indicated. DMSO (0.1%) treated cells served as internal control. Values are shown as mean±SD after normalizing with the corresponding protein content and expressed relative to basal of control cells which was set to 1; *p < 0.05, **p < 0.01, versus corresponding control cells , bp < 0.005 versus corresponding Simvastatin treated cells (two way ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561915&req=5

f3: Simvastatin does not impair PPAR-γ mediated glucose uptake: Mean basal and insulin stimulated (5 min and 10 min) uptake of 2-NBDG by L6 myotubes treated with Simvastatin (1 μM) and/or Pioglitazone (10 μM) for different time points as indicated. DMSO (0.1%) treated cells served as internal control. Values are shown as mean±SD after normalizing with the corresponding protein content and expressed relative to basal of control cells which was set to 1; *p < 0.05, **p < 0.01, versus corresponding control cells , bp < 0.005 versus corresponding Simvastatin treated cells (two way ANOVA).
Mentions: Cells were treated either with simvastatin or pioglitazone alone or with a combination of the two drugs. Pioglitazone is a known PPAR gamma activator. As shown in Fig. 3, simvastatin alone had little effect on non-insulin stimulated glucose uptake. But combination of simvastatin with pioglitazone or pioglitazone alone showed substantial (~200% compared to DMSO treated control cells) increase in glucose uptake.

Bottom Line: Statins are a class of oral drugs that are widely used for treatment of hypercholesterolemia.We explored the possible mechanism of statin induced insulin resistance using a well-established cell based model and simvastatin as a prototype statin.Our data show that simvastatin induces insulin resistance in a cholesterol biosynthesis inhibition independent fashion but does so by a fatty acid mediated effect on insulin signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.

ABSTRACT
Statins are a class of oral drugs that are widely used for treatment of hypercholesterolemia. Recent clinical data suggest that chronic use of these drugs increases the frequency of new onset diabetes. Studies to define the risks of statin-induced diabetes and its underlying mechanisms are clearly necessary. We explored the possible mechanism of statin induced insulin resistance using a well-established cell based model and simvastatin as a prototype statin. Our data show that simvastatin induces insulin resistance in a cholesterol biosynthesis inhibition independent fashion but does so by a fatty acid mediated effect on insulin signaling pathway. These data may help design strategies for prevention of statin induced insulin resistance and diabetes in patients with hypercholesterolemia.

No MeSH data available.


Related in: MedlinePlus