Role of the ubiquitin-proteasome system and autophagy in regulation of insulin sensitivity in serum-starved 3T3-L1 adipocytes.
Role of the ubiquitin-proteasome system and autophagy in regulation of insulin sensitivity in serum-starved 3T3-L1 adipocytes.
复制标题
泛素蛋白酶体系统和自噬在血清饥饿 3T3-L1 脂肪细胞胰岛素敏感性调节中的作用。
DOI：
10.1507/endocrj.ej15-0030
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发表时间：
2015-05
影响因子：
2
通讯作者：
Wang, Changhua
中科院分区：
文献类型：
--
作者：
Chen, Leyuan Jack;Li, Mingxin;Tang, Zhao;Wang, Changhua
泛素-蛋白酶体系统（UPS）和自噬是两种保守的细胞内蛋白水解途径，负责活细胞中大多数细胞蛋白的降解。目前，UPS和自噬都被认为与胰岛素抵抗和糖尿病的发病机制有关。然而，其潜在机制在很大程度上仍然未知。本研究的目的是研究UPS和自噬对血清饥饿的3 T3-L1脂肪细胞胰岛素敏感性的影响。我们的研究结果表明，血清耗竭导致UPS和自噬的激活，伴随着胰岛素敏感性的增加。硼替佐米（BZM），一种高度选择性的，可逆的26 S蛋白酶体抑制剂抑制UPS诱导自噬的代偿性激活，但不影响显着的胰岛素作用。自噬的遗传和药理学抑制显著减轻了血清饥饿升高的胰岛素敏感性。此外，自噬抑制损害UPS功能，并导致内质网（ER）应激和未折叠蛋白反应（UPR）。BMZ对UPS的抑制加重了自噬抑制诱导的ER应激和UPR。这些结果表明，UPS和自噬维持的蛋白质质量控制是保持胰岛素敏感性所必需的。重要的是，自噬的适应性激活在3 T3-L1脂肪细胞中血清饥饿诱导的胰岛素增敏中起关键作用。
The ubiquitin-proteasome system (UPS) and autophagy are two conserved intracellular proteolytic pathways, responsible for degradation of most cellular proteins in living cells. Currently, both the UPS and autophagy have been suggested to be associated with pathogenesis of insulin resistance and diabetes. However, underlying mechanism remains largely unknown. The purpose of the present study is to investigate the impact of the UPS and autophagy on insulin sensitivity in serum-starved 3T3-L1 adipocytes. Our results show that serum depletion resulted in activation of the UPS and autophagy, accompanied with increased insulin sensitivity. Inhibition of the UPS with bortezomib (BZM), a highly selective, reversible 26S proteasome inhibitor induced compensatory activation of autophagy but did not affect significantly insulin action. Genetic and pharmacological inhibition of autophagy dramatically mitigated serum starvation-elevated insulin sensitivity. In addition, autophagy inhibition compromised UPS function and led to endoplasmic reticulum (ER) stress and unfolded protein response (UPR). Inability of the UPS by BMZ exacerbated autophagy inhibition-induced ER stress and UPR. These results suggest that protein quality control maintained by the UPS and autophagy is required for preserving insulin sensitivity. Importantly, adaptive activation of autophagy plays a critical role in serum starvation-induced insulin sensitization in 3T3-L1 adipocytes.
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影响因子：
7.7
作者：
Otoda T;Takamura T;Misu H;Ota T;Murata S;Hayashi H;Takayama H;Kikuchi A;Kanamori T;Shima KR;Lan F;Takeda T;Kurita S;Ishikura K;Kita Y;Iwayama K;Kato K;Uno M;Takeshita Y;Yamamoto M;Tokuyama K;Iseki S;Tanaka K;Kaneko S
通讯作者：
Kaneko S
影响因子：
--
作者：
K. Soumaya
通讯作者：
K. Soumaya
影响因子：
3.5
作者：
Fujita, Eriko;Kouroku, Yoriko;Momoi, Takashi
通讯作者：
Momoi, Takashi
影响因子：
4.8
作者：
Jansen, H. J.;van Essen, P.;Stienstra, R.
通讯作者：
Stienstra, R.
影响因子：
4.1
作者：
Fuertes, G;De Llano, JJM;Knecht, E
通讯作者：
Knecht, E