SUR2a gene is upregulated in skeletal muscle insulin resistance of obese rats: correlation with GLUT4 gene
M. Felipe dos Santos Ferreira Marques, R. Cristina Tieko Mori, M. Mitiko Okamoto & U. Fabres Machado
Objective: The aim of this study was to investigate whether SUR2A (sulfonylurea receptor type 2A, ABCC9) MEF2a (myocyte enhancer factor-2a) and HIF1a (Hypoxia-inducible factor-1) can influence glucose uptake in oxidative muscle soleus by regulating GLUT4 expression.
Methods: Insulin resistance was induced in male Wistar rats by inducing obesity with monosodium glutamate (MSG). At the age 3 months, half control and MSG-treated animals started receiving 0.1 mg/kg/day of glimepiride in the drinking water, and distributed in 3 experimental groups: control rats (C), MSG-obese rats (O) and MSG-obese rats treated with glimepiride (OG). Animals were submitted to insulin tolerance test (ITT) and samples of soleus muscle were excised for quantification of gene expression by Real Time RT-PCR and GLUT4 protein.
Results: OG rats presented a ~51% increase in SUR2A mRNA content in comparison to O and C rats (P<0.001). O rats showed 16% increase in GLUT4 mRNA content (P<0.01 vs C), without any increase in GLUT4 protein. After glimepiride treatment, OG rats increased GLUT4 mRNA (21%, P<0.01 vs C) and protein (131%, P<0.01 vs C; and 73%, P<0.05 vs O). No significant differences (P>0.05) in mRNA expression of MEF2a and HIF1a were found.
Conclusion: We conclude that the glimepiride increased the GLUT4 expression in soleus of the insulin resistant animals which could be associated to SUR2A genes expression.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.