Interference with Akt signaling pathway contributes curcumin-induced adipocyte insulin resistance.
Previous study has shown that curcumin directly or indirectly suppresses insulin signaling in 3T3-L1 adipocytes. However, the underlying mechanism remains unclear. Here we experimentally demonstrate that curcumin inhibited the ubiquitin-proteasome system (UPS) function, activated autophagy, and reduced protein levels of protein kinase B (Akt) in a dose- and time-dependent manner in 3T3-L1 adipocytes, accompanied with attenuation of insulin-stimulated Akt phosphorylation, plasma membrane translocation of glucose transporter type 4 (GLUT4), and glucose uptake. These in vitro inhibitory effects of curcumin on Akt protein expression and insulin action were reversed by pharmacological and genetic inhibition of autophagy but not by inhibition of the UPS and caspases. In addition, Akt reduction in adipose tissues of mice treated with curcumin could be recovered by administration of autophagy inhibitor bafilomycin A1 (BFA). This new finding provides a novel mechanism by which curcumin induces insulin resistance in adipocytes.
Department of Pathology & Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
Deling
D
Zhang
Department of Pathology & Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
Yemin
Y
Zhang
Department of Endocrinology, The Central Hospital of Enshi Autonomous Prefecture, Enshi 445000, China.
Mao
M
Ye
Department of Hepatobiliary & Laparascopic Surgery, Wuhan University Renmin Hospital, Wuhan 430060, China.
Youming
Y
Ding
Department of Pathology & Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
Zhao
Z
Tang
Department of Pathology & Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
Mingxin
M
Li
Department of Hepatobiliary & Laparascopic Surgery, Wuhan University Renmin Hospital, Wuhan 430060, China.
Yu
Y
Zhou
Department of Pathology & Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China. Electronic address: chwang0525@whu.edu.cn.
Changhua
C
Wang
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D000071187:Autophagy-Related Protein 5 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D004795:Enzyme Stability / Q000187:drug effects; D055785:Gene Knockdown Techniques; D007333:Insulin Resistance; D008810:Mice, Inbred C57BL; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology; D059748:Proteolysis / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D025801:Ubiquitin / Q000378:metabolism
C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D061945:Caspase Inhibitors; D061988:Proteasome Inhibitors; D025801:Ubiquitin; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases; D046988:Proteasome Endopeptidase Complex; D003474:Curcumin
Adipocytes; Autophagy; Curcumin; Protein kinase B; Ubiquitin proteasome system