Effect of a novel non-thiazolidinedione peroxisome proliferator-activated receptor alpha/gamma agonist on glucose uptake
文献类型：期刊论文
| 作者 | Hu, X.; Feng, Y.; Liu, X. ; Zhao, X. -F.; Yu, J. -H.; Yang, Y. -S.; Sydow-Backman, M.; Horling, J.; Zierath, J. R.; Leng, Y.
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| 刊名 | DIABETOLOGIA
 |
| 出版日期 | 2007-05 |
| 卷号 | 50期号:5页码:1048-1057 |
| ISSN号 | 0012-186X |
| 关键词 | adipose tissue diet-induced obesity glucose uptake insulin sensitivity insulin signalling peroxisome proliferator-activated receptors skeletal muscle thiazolidinediones |
| DOI | 10.1007/s00125-007-0622-3 |
| 文献子类 | Article |
| 英文摘要 | Aims/hypothesis The effect of the benzopyran derivative T33, a novel non-thiazolidinedione agent, was studied on peroxisome proliferator-activated receptors (PPARs), insulin signalling and glucose uptake in adipocytes and skeletal muscle. We hypothesised that T33 could activate PPAR gamma and exert a beneficial effect on insulin action on glucose uptake and lipid metabolism. Materials and methods Using a cell-based reporter gene assay, T33 was identified as a PPAR alpha/gamma dual agonist, which activated human PPAR gamma and PPAR alpha with EC50 values of 19 and 148 nmol/l, respectively. The effect of T33 on glucose metabolism was studied in cultured 3T3-L1 adipocytes and L6 myotubes. In vivo effects of T33 on skeletal muscle were determined in ob/ob mice treated with 8 mg/kg T33. The effect of T33 on metabolic abnormalities was observed in diet-induced obese mice. Results Exposure of 3T3-L1 adipocytes to T33 for 4 days increased basal and insulin-stimulated glucose uptake, with no effect noted in L6 myotubes. Treatment of ob/ob mice for 20 days with T33 normalised basal and insulin-stimulated glucose uptake and increased phosphorylation of Akt and p38 mitogen-activated protein kinase in skeletal muscle. In contrast, phosphorylation of AMP-activated protein kinase was unaltered. Moreover, T33 improved insulin sensitivity and lipid metabolism in diet-induced obese mice. Conclusions/interpretation T33 is non-thiazolidinedione PPAR alpha/gamma dual agonist which directly increases basal and insulin-stimulated glucose uptake in adipocytes and secondarily improves insulin action on insulin signalling and glucose metabolism in skeletal muscle from diabetic ob/ob mice. |
| WOS关键词 | PPAR-GAMMA ; 3T3-L1 ADIPOCYTES ; SKELETAL-MUSCLE ; INSULIN-RESISTANCE ; OB/OB MICE ; TRANSPORT ; DISEASE ; ALPHA ; ROSIGLITAZONE ; EXERCISE |
| WOS研究方向 | Endocrinology & Metabolism |
| 语种 | 英语 |
| 出版者 | SPRINGER |
| WOS记录号 | WOS:000245521400021 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273271]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Leng, Y. |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China 2.Karolinska Inst, Dept Mol Med & Surg Sci, Sect Integrat Physiol, Stockholm, Sweden 3.Biovitrum AB, Stockholm, Sweden |
| 推荐引用方式 GB/T 7714 | Hu, X.,Feng, Y.,Liu, X.,et al. Effect of a novel non-thiazolidinedione peroxisome proliferator-activated receptor alpha/gamma agonist on glucose uptake[J]. DIABETOLOGIA,2007,50(5):1048-1057. |
| APA | Hu, X..,Feng, Y..,Liu, X..,Zhao, X. -F..,Yu, J. -H..,...&Leng, Y..(2007).Effect of a novel non-thiazolidinedione peroxisome proliferator-activated receptor alpha/gamma agonist on glucose uptake.DIABETOLOGIA,50(5),1048-1057. |
| MLA | Hu, X.,et al."Effect of a novel non-thiazolidinedione peroxisome proliferator-activated receptor alpha/gamma agonist on glucose uptake".DIABETOLOGIA 50.5(2007):1048-1057. |
入库方式： OAI收割
来源：上海药物研究所
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