Effect of simvastatin on burn-induced alterations in tissue specific glucose metabolism: implications for burn associated insulin resistance

  • Authors:
    • Ali A. Bonab
    • Edward A. Carter
    • Kasie Paul
    • Masao Kaneki
    • Yong-Ming Yu
    • Ronald G. Tompkins
    • Alan J. Fischman
  • View Affiliations

  • Published online on: September 1, 2010     https://doi.org/10.3892/ijmm_00000467
  • Pages: 311-316
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Abstract

In addition to their primary role in lowering plasma cholesterol, statins have a variety of other actions. We studied the effect of simvastatin treatment on burn injury-induced changes in regional glucose metabolism. Groups of six CD-1 mice (male, ≈25 g) were subjected to full thickness 30% total body surface area (TBSA) burn injury. The animals were treated with simvastatin at various doses (0.02, 0.2 and 2.0 µg/kg, i.p.) for seven days. The following morning, mice were injected with 18F labeled 2-fluoro-2-deoxy-D-glucose (18FDG) (50 µCi) via the tail vein. Approximately 60 min after tracer injection, the animals were sacrificed and biodistribution was measured. A sub-set of burned mice with and without statin treatment and sham controls was injected with ≈1.0 mCi of FDG and tracer distribution was evaluated by µPET. In addition, oral glucose tolerance tests (OGTT) were performed in other groups of burned mice with and without statin treatment and sham controls. In the heart and brown adipose tissue (BAT), burn injury produced a highly significant increase in 18FDG accumulation (p<0.01), whereas tracer accumulation in brain was markedly reduced (p<0.01). In the heart and BAT, simvastatin treatment produced dose-dependent reductions in 18FDG accumulation. In contrast, simvastatin did not affect 18FDG accumulation in the brain. There was no effect of simvastatin treatment on 18FDG accumulation in the heart, BAT or brain of sham-treated mice. Less pronounced effects were detected in other tissues that were studied. All animals had normal plasma glucose levels (≈90 mg/dl). The OGTTs demonstrated insulin resistance in burn injured mice which was reversed by statin treatment. Our results indicate that simvastatin reverses burn-induced increases in 18FDG accumulation by the heart and BAT in a dose-dependent manner but does not affect burn-induced reductions of 18FDG accumulation by the brain. These findings suggest that statins exert some of their effects by tissue specific modulation of glucose metabolism.

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September 2010
Volume 26 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Bonab AA, Carter EA, Paul K, Kaneki M, Yu Y, Tompkins RG and Fischman AJ: Effect of simvastatin on burn-induced alterations in tissue specific glucose metabolism: implications for burn associated insulin resistance . Int J Mol Med 26: 311-316, 2010
APA
Bonab, A.A., Carter, E.A., Paul, K., Kaneki, M., Yu, Y., Tompkins, R.G., & Fischman, A.J. (2010). Effect of simvastatin on burn-induced alterations in tissue specific glucose metabolism: implications for burn associated insulin resistance . International Journal of Molecular Medicine, 26, 311-316. https://doi.org/10.3892/ijmm_00000467
MLA
Bonab, A. A., Carter, E. A., Paul, K., Kaneki, M., Yu, Y., Tompkins, R. G., Fischman, A. J."Effect of simvastatin on burn-induced alterations in tissue specific glucose metabolism: implications for burn associated insulin resistance ". International Journal of Molecular Medicine 26.3 (2010): 311-316.
Chicago
Bonab, A. A., Carter, E. A., Paul, K., Kaneki, M., Yu, Y., Tompkins, R. G., Fischman, A. J."Effect of simvastatin on burn-induced alterations in tissue specific glucose metabolism: implications for burn associated insulin resistance ". International Journal of Molecular Medicine 26, no. 3 (2010): 311-316. https://doi.org/10.3892/ijmm_00000467