3,3'-Diindolylmethane Enhances Glucose Uptake Through Activation of Insulin Signaling in 3T3-L1 Adipocytes

Obesity (Silver Spring). 2018 Jul;26(7):1153-1160. doi: 10.1002/oby.22145. Epub 2018 May 3.

Abstract

Objective: Indole-3-carbinol (I3C), a naturally occurring compound found in cruciferous vegetables, and its metabolite 3,3'-diindolylmethane (DIM) reduce body mass and serum glucose levels in high-fat-diet-induced obese mice. This study aimed to determine whether I3C or DIM could increase glucose uptake via enhanced insulin sensitivity in 3T3-L1 adipocytes, as well as the mechanism involved.

Methods: 3T3-L1 preadipocytes were differentiated by using a mixture of adipogenic inducers, including a suboptimal concentration of insulin.

Results: DIM, but not I3C, increased adipocyte differentiation through upregulation of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α. DIM also enhanced glucose uptake by increasing expression of glucose transporter 4 in adipocytes. This was associated with DIM-enhanced phosphorylation of the signaling intermediates Akt, insulin receptor substrate-1, and insulin receptor early in differentiation.

Conclusions: Our findings suggest that DIM may improve insulin sensitivity through the activation of the insulin signaling pathway, leading to enhanced glucose uptake.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism*
  • Adipocytes / physiology
  • Adipogenesis / drug effects
  • Adipogenesis / genetics
  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Gene Expression Regulation / drug effects
  • Glucose / pharmacokinetics*
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism
  • Indoles / pharmacology*
  • Insulin / metabolism*
  • Mice
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • Glucose Transporter Type 4
  • Indoles
  • Insulin
  • Slc2a4 protein, mouse
  • Glucose
  • 3,3'-diindolylmethane