SUR2a gene is upregulated in skeletal muscle insulin resistance of obese rats: possible correlation with GLUT4 gene

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.