Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, 05508-900 São Paulo, Brazil.
Diabetol Metab Syndr. 2015 Mar 14;7:18. doi: 10.1186/s13098-015-0015-6. eCollection 2015.
Decreased expression of glucose transporter protein GLUT4, encoded by the solute carrier 2A4 (Slc2a4) gene, is involved in obesity-induced insulin resistance. Local tissue inflammation, by nuclear factor-κB (NFκB)-mediated pathway, has been related to Slc2a4 repression; a mechanism that could be modulated by statins. Using a model of obesity with insulin resistance, this study investigated whether (1) inflammatory markers and Slc2a4 expression are altered; (2) atorvastatin has beneficial effects on inflammation and Slc2a4 expression; and (3) inhibitor of NFκB (IKK)/NFκB pathway is involved in subcutaneous adipose tissue (SAT).
Obese mice showed insulin resistance, decreased expression of Slc2a4 mRNA (66%, P < 0.01) and GLUT4 protein (30%, P < 0.05), and increased expression of interleukin 6 (Il6) mRNA (44%, P < 0.05) in SAT. Obese mice treated with atorvastatin had enhanced in vivo insulin sensitivity, besides increased Slc2a4/GLUT4 expression and reduced Il6 expression in SAT. No alterations of tumor necrosis factor-α, interleukin 1β and adiponectin expression or IKKα/β activity in SAT of obese mice or obese mice treated with atorvastatin were observed.
Atorvastatin has beneficial effect upon glycemic homeostasis, which may be related to its positive impact on Il6 and Slc2a4/GLUT4 expression in SAT.
葡萄糖转运蛋白 GLUT4 的表达减少，其由溶质载体 2A4（Slc2a4）基因编码，与肥胖引起的胰岛素抵抗有关。通过核因子-κB（NFκB）介导的途径，局部组织炎症与 Slc2a4 的抑制有关；这种机制可以被他汀类药物调节。使用肥胖伴胰岛素抵抗的模型，本研究调查了（1）炎症标志物和 Slc2a4 表达是否改变；（2）阿托伐他汀是否对炎症和 Slc2a4 表达有有益影响；（3）NFκB 抑制剂（IKK）/NFκB 途径是否参与皮下脂肪组织（SAT）。
肥胖小鼠表现出胰岛素抵抗，SAT 中 Slc2a4 mRNA 表达减少（66%，P<0.01）和 GLUT4 蛋白减少（30%，P<0.05），白细胞介素 6（Il6）mRNA 表达增加（44%，P<0.05）。阿托伐他汀治疗的肥胖小鼠体内胰岛素敏感性增强，同时 SAT 中 Slc2a4/GLUT4 表达增加，Il6 表达减少。肥胖小鼠或阿托伐他汀治疗的肥胖小鼠的肿瘤坏死因子-α、白细胞介素 1β和脂联素表达或 SAT 中 IKKα/β活性没有改变。
阿托伐他汀对血糖稳态有有益的影响，这可能与其对 SAT 中 Il6 和 Slc2a4/GLUT4 表达的积极影响有关。
