Glimepiride improves insulin sensitivity in oxidative skeletal muscle of obese rats: possible association between GLUT4 and SUR2A expressions
M F S F M Felipe dos Santos Ferreira Marques, R C T M Cristina Tieko Mori, M M O Mitiko Okamoto & U F M Fabres Machado
Studies have demonstrated that ATP-sensitive potassium channel (KATP) subunits SUR2A (sulfonylurea receptor) and KIR6.2 are involved in glucose uptake into skeletal muscle. It is known that the glucose transporter 4 (GLUT4) expression is highest in oxidative type I fibers, pointing out the important role of oxidative muscles as glucose uptakes. Considering these aspects the aim of this study was to investigate whether KATP channel can influence glucose uptake in oxidative muscle soleus by regulating GLUT4 expression. Insulin resistance was induced in male Wistar rats by inducing obesity with monosodium glutamate (MSG) (4 mg/g per day). At the age 3 months, half control and MSG-treated animals started receiving 0.1 mg/kg per day of glimepiride in the drinking water, and distributed in 4 groups: control rats (C), control rats treated with glimepiride (OG), 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 SUR2A, KIR6.2 and GLUT4 mRNA expression and GLUT4 protein. In ITT, O rats showed 33% decrease in glucose decay constant (kITT) in response to insulin (P<0.05 versus C and OG) and the glimepiride treatment made the kITT value return to the control level. OG rats presented a ~48% increase in SUR2A mRNA content in comparison to O and C rats (P<0.01). O rats showed 16% increase in GLUT4 mRNA content (P<0.01 versus C), without any increase in GLUT4 protein. After glimepiride treatment, OG rats increased GLUT4 mRNA (19%, P<0.01 versus C) and protein (159%, P<0.01 versus C; and 78%, P<0.05 versus O). Obesity or glimepiride treatment did not alter KIR6.2 mRNA content. We conclude that the glimepiride increased the GLUT4 expression in soleus of the insulin resistant animals which could be associated to SUR2A genes expression, playing an important role in the maintenance of the glycemic homeostasis.