Role of the ubiquitin-proteasome system and autophagy in regulation of insulin sensitivity in serum-starved 3T3-L1 adipocytes

Endocrine Journal

Zhao Tang³  Leyuan Jack Chen²  Yemin Zhang³  Changhua Wang³  Mao Ye¹  Mingxin Li³ 

[1] Department of Endocrinology, The Central Hospital of Enshi Autonomous Prefecture, Enshi 445000, China;School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA;Department of Pathology & Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China

关键词: Autophagy;    Ubiquitin-proteasome system;    Insulin sensitivity;    Adipocytes;   

DOI  :  10.1507/endocrj.EJ15-0030

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(50)Cited-By(2)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.

【 授权许可】

Unknown