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Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
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Interference with Akt signaling pathway contributes curcumin-induced adipocyte insulin resistance

Deling Zhang1, Yemin Zhang1, Mao Ye2

  • 1Department of Pathology & Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.

Molecular and Cellular Endocrinology
|April 27, 2016
PubMed

Insights

Curcumin induces insulin resistance by activating autophagy and reducing Akt protein in fat cells. Inhibiting autophagy reverses these effects, revealing a novel mechanism for curcumin-induced insulin resistance.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Metabolic Research

Background:

  • Curcumin is known to affect insulin signaling, but the precise mechanism leading to insulin resistance is not fully understood.
  • Previous studies suggest curcumin's impact on insulin signaling pathways in adipocytes.
  • Elucidating the molecular mechanisms behind curcumin's effects is crucial for understanding metabolic health.

Purpose of the Study:

  • To investigate the underlying mechanism by which curcumin suppresses insulin signaling in 3T3-L1 adipocytes.
  • To determine the role of the ubiquitin-proteasome system (UPS) and autophagy in curcumin-induced insulin resistance.
  • To explore the impact of curcumin on Akt protein levels and insulin action.

Main Methods:

  • Experimental analysis of curcumin's effects on 3T3-L1 adipocytes and mouse adipose tissue.
  • Assessment of ubiquitin-proteasome system (UPS) function and autophagy activation.
  • Measurement of protein kinase B (Akt) levels, Akt phosphorylation, and glucose transporter type 4 (GLUT4) translocation.
  • Utilizing pharmacological and genetic inhibition of autophagy and UPS.

Main Results:

  • Curcumin inhibited UPS function, activated autophagy, and reduced Akt protein levels in a dose- and time-dependent manner.
  • Curcumin attenuated insulin-stimulated Akt phosphorylation, GLUT4 translocation, and glucose uptake.
  • Inhibition of autophagy, but not UPS or caspases, reversed curcumin's inhibitory effects on Akt and insulin action.
  • Autophagy inhibition (bafilomycin A1) restored Akt levels in curcumin-treated mouse adipose tissue.

Conclusions:

  • Curcumin induces insulin resistance in adipocytes primarily by activating autophagy, leading to reduced Akt protein levels.
  • Autophagy is a key mediator of curcumin's negative effects on insulin signaling and glucose uptake.
  • This study reveals a novel mechanism for curcumin-induced insulin resistance, highlighting autophagy as a potential therapeutic target.
Keywords:
AdipocytesAutophagyCurcuminProtein kinase BUbiquitin proteasome system

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