A PPAR agonist improves TNF-α-induced insulin resistance of adipose tissue in mice
A PPAR agonist improves TNF-α-induced insulin resistance of adipose tissue in mice
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PPAR 激动剂改善 TNF-α 诱导的小鼠脂肪组织胰岛素抵抗
DOI：
10.1016/j.bbrc.2003.07.007
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发表时间：
2003
影响因子：
3.1
通讯作者：
Y. Saito
中科院分区：
文献类型：
--
作者：
M. Shibasaki;K. Takahashi;T. Itou;H. Bujo;Y. Saito
噻唑烷二酮类（TZDs），PPARs激动剂，已被证明可以阻断TNF-α对培养细胞胰岛素作用的抑制作用。为了阐明TZD对TNF-α抑制胰岛素敏感性的体内作用，在TNF-α过表达小鼠模型中使用分泌TNF-α蛋白的细胞移植评估了肌肉和脂肪组织中的胰岛素作用。吡格列酮治疗4周后，分析葡萄糖摄取、胰岛素诱导的IRS-1磷酸化和脂蛋白脂酶mRNA水平。通过OGTT评估，吡格列酮未改善该模型中TNF-α诱导的高胰岛素血症。TNF-α过表达小鼠脂肪组织中TNF-α可降低葡萄糖摄取和脂蛋白脂酶mRNA水平，吡格列酮可阻断TNF-α的这些抑制作用。另一方面，在肌肉中，吡格列酮未逆转TNF-α对胰岛素诱导的IRS-1磷酸化、葡萄糖摄取和脂蛋白脂肪酶mRNA水平的影响。目前的研究揭示了在TNF-α过度表达模型中，使用细胞移植恢复降低的胰岛素作用对吡格列酮的不同敏感性。这些结果表明，TZDs的效果取决于人体内脂肪的分布和积累。
Thiazolidinediones (TZDs), agonists for PPARs, have been shown to block the inhibitory effects of TNF-α on insulin action using cultured cells. In order to clarify the in vivo effects of TZDs on the inhibition of insulin sensitivity by TNF-α, insulin action in muscles and adipose tissues was assessed in the TNF-α-overexpression mice model using transplantation of cells secreting the TNF-α protein. After the pioglitazone treatment for 4 weeks, glucose uptake, insulin-induced IRS-1 phosphorylation, and lipoprotein lipase mRNA levels were analyzed. Pioglitazone did not ameliorate TNF-α-induced hyperinsulinemia in this model, as assessed by the OGTT. Glucose uptake and lipoprotein lipase mRNA levels were decreased by TNF-α in adipose tissues from the TNF-α-overexpressing mice, and pioglitazone blocked these inhibitions by TNF-α. On the other hand, in muscles, pioglitazone did not reverse the effects of TNF-α on insulin-induced phosphorylation of IRS-1, glucose uptake, and lipoprotein lipase mRNA levels. Present study revealed the different sensitivities of pioglitazone for the recovery of decreased insulin action in a TNF-α-overexpressing model using cell transplantation. These results suggest that the effect of TZDs is dependent on the fat distribution and accumulation in humans.
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影响因子：
15.9
作者：
Peraldi, P;Xu, M;Spiegelman, BM
通讯作者：
Spiegelman, BM
DOI：
10.1073/pnas.91.11.4854
发表时间：
1994-05-24
影响因子：
11.1
作者：
HOTAMISLIGIL, GS;MURRAY, DL;SPIEGELMAN, BM
通讯作者：
SPIEGELMAN, BM
影响因子：
4.8
作者：
A. Chawla;E. Schwarz;D. Dimaculangan;M. Lazar
通讯作者：
A. Chawla;E. Schwarz;D. Dimaculangan;M. Lazar
影响因子：
15.9
作者：
KERN, PA;SAGHIZADEH, M;SIMSOLO, RB
通讯作者：
SIMSOLO, RB