Direct inhibitory effects of pioglitazone on hepatic fetuin-A expression.
Direct inhibitory effects of pioglitazone on hepatic fetuin-A expression.
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DOI：
10.1371/journal.pone.0088704
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Inaba M
中科院分区：
文献类型：
--
作者：
Ochi A;Mori K;Emoto M;Nakatani S;Morioka T;Motoyama K;Fukumoto S;Imanishi Y;Koyama H;Ishimura E;Inaba M
胎球蛋白-A是一种在肝脏中合成的循环糖蛋白，与胰岛素抵抗和2型糖尿病有关。然而，胎球蛋白-A合成的调节仍然是模糊的。我们以前报道过吡格列酮治疗能显著降低2型糖尿病患者血清胎球蛋白A水平。为了阐明吡格列酮是否可以直接抑制肝胎球蛋白A的合成，我们研究了吡格列酮对胎球蛋白A表达的影响，在体外和体内。吡格列酮处理抑制Fao肝癌细胞中胎球蛋白-A的mRNA和蛋白表达。有趣的是，罗格列酮而不是二甲双胍也抑制胎球蛋白-A的表达。此外，GW 9662（过氧化物酶体增殖物激活受体（PPAR）γ的抑制剂）逆转了吡格列酮诱导的胎球蛋白A抑制，这表明噻唑烷二酮衍生物可能在胎球蛋白A抑制方面具有共同特征，可能通过PPARγ激活。最后，小鼠经口给予吡格列酮8周导致肝胎球蛋白-A mRNA抑制。这些结果表明，吡格列酮可能通过直接抑制肝脏中胎球蛋白-A的表达而部分改善胰岛素抵抗。
Fetuin-A, a circulating glycoprotein synthesized in the liver, is involved in insulin resistance and type 2 diabetes. However, regulation of fetuin-A synthesis has remained obscure. We previously reported that pioglitazone treatment significantly reduced serum fetuin-A levels in patients with type 2 diabetes. To clarify whether pioglitazone can directory inhibit hepatic fetuin-A synthesis, we investigated the effects of pioglitazone on fetuin-A expression both in vitro and in vivo. Pioglitazone treatment suppressed mRNA and protein expression of fetuin-A in Fao hepatoma cells. Interestingly, rosiglitazone but not metformin, also inhibited fetuin-A expression. In addition, GW 9662, an inhibitor of peroxisome proliferator-activated receptor (PPAR) γ, reversed pioglitazone-induced suppression of fetuin-A, suggesting that thiazolidinedione derivatives may have common characteristics with regard to fetuin-A suppression, possibly through PPARγactivation. Finally, oral administration of pioglitazone to mice for 8 weeks resulted in suppression of hepatic fetuin-A mRNA. These findings suggest that pioglitazone may partially ameliorate insulin resistance through its direct inhibitory effects on fetuin-A expression in the liver.
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影响因子：
7.7
作者：
Monden M;Koyama H;Otsuka Y;Morioka T;Mori K;Shoji T;Mima Y;Motoyama K;Fukumoto S;Shioi A;Emoto M;Yamamoto Y;Yamamoto H;Nishizawa Y;Kurajoh M;Yamamoto T;Inaba M
通讯作者：
Inaba M
影响因子：
7.7
作者：
Stefan, Norbert;Fritsche, Andreas;Weikert, Cornelia;Boeing, Heiner;Joost, Hans-Georg;Haring, Hans-Ulrich;Schulze, Matthias B.
通讯作者：
Schulze, Matthias B.
影响因子：
4.8
作者：
Heiss, A;DuChesne, A;Jahnen-Dechent, W
通讯作者：
Jahnen-Dechent, W
影响因子：
16.2
作者：
Stefan, N;Hennige, AM;Häring, HU
通讯作者：
Häring, HU
影响因子：
15.9
作者：
Matsusue, K;Haluzik, M;Gonzalez, FJ
通讯作者：
Gonzalez, FJ