Inhibition of Lipid Infusion–Induced Skeletal Muscle Insulin Resistance by Cotreatment With Tempol and Glutathione in Mice

Journal of Pharmacological Sciences

Byung Seok Kim²  Hye-Na Cha¹  Jin-Myoung Dan³  Yong-Woon Kim¹  Jong-Yeon Kim¹  So-Young Park¹ 

[1] Department of Physiology, College of Medicine, Yeungnam University, Korea;Department of Internal Medicine, Catholic University of Daegu, Korea;Department of Orthopedic Surgery, Gumi CHA University Hospital, Korea

关键词: insulin resistance;    lipid;    oxidative stress;    skeletal muscle;    inflammation;   

DOI  :  10.1254/jphs.09046FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(48)Cited-By(13)In the present study, we examined whether lipid infusion–induced insulin resistance in skeletal muscle could be reversed by the antioxidants tempol, glutathione (GSH), or tempol with GSH in male C57BL/6J mice via hyperinsulinemic-euglycemic clamp. Lipid infusion increased the mRNA level of mitochondrial type superoxide dismutase (Mn-SOD), glutathione peroxidase 1, tumor necrosis factor-α, and interleukin-6. Lipid infusion decreased GSH and GSH/glutathione disulfide (GSSG) ratio and increased the activities of JNK and p38 in skeletal muscle. Lipid infusion induced insulin resistance in whole body and skeletal muscle. Treatment with the SOD mimetic tempol did not prevent oxidative stress, the inflammatory response, and insulin resistance induced by lipid infusion. Tempol alone increased oxidative stress and aggravated the lipid-induced inflammatory response. GSH at 100 and 200 μmol · kg−1 · h−1 did not prevent insulin resistance and the inflammatory response by lipid infusion. On the contrary, GSH at 100 μmol · kg−1 · h−1 with tempol prevented insulin resistance in the whole body and skeletal muscle, and it completely reversed oxidative stress and the inflammatory response. These results suggest that lipid infusion–induced insulin resistance in skeletal muscle is produced by oxidative stress and cotreatment with tempol and GSH inhibits lipid-induced insulin resistance.

【 授权许可】

Unknown