Jateorhizine alleviates insulin resistance by promoting adipolysis and glucose uptake in adipocytes

J Recept Signal Transduct Res. 2021 Jun;41(3):255-262. doi: 10.1080/10799893.2020.1806319. Epub 2020 Aug 18.

Abstract

Jateorhizine (Jat) can reduce blood glucose in diabetic mice, but there are few studies on its role in insulin resistance (IR). This study analyzed the effect of Jat on adipocytes, so as to provide an evidence for the clinical application of Jat. MDI was used to differentiate preadipocytes into adipocytes and induce IR cell models. Different concentrations of Jat (1, 5, 10, 20 μmol/L) were added into undifferentiated and differentiated cells. The cell viability was detected using MTT method. Oil red O staining was performed to observe the lipid formation in cells. Adipolysis method was used to detect the release of glycerol in cell culture medium. The level of 2-DG in cells was detected by glucose uptake assay based on insulin treatment. The expression of adipose transcription factors and IRS2/p-PI3K/p-AKT/GLUT4 signaling pathway was analyzed by western blot (WB) analysis. Neither the activity of differentiated nor undifferentiated preadipocytes was affected by the addition of Jat. There was numerous lipid formation in cells induced by MDI, which was decreased visibly by Jat. Jat reduced the expression levels of MDI-induced elevated levels of PPARγ, C/EBPα, FABP4, perilipin and FAS, as well as increased the release of glycerol in adipocytes. Moreover, Jat further enhanced the 2-DG uptake in MDI-induced adipocytes, and activated the IRS2/p-PI3K/p-AKT/GLUT4 signaling pathway. In general, the role of Jat in adipocytes was concentration-dependent. Jat can not only promote adipolysis, but also increase the glucose uptake in adipocytes, which might be a potential therapy for IR.

Keywords: Insulin resistance; adipocytes; adipolysis; glucose uptake; jateorhizine.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Animals
  • Berberine / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Gene Expression Regulation / drug effects
  • Glucose / metabolism*
  • Glucose Transporter Type 4 / metabolism
  • Insulin Receptor Substrate Proteins / metabolism
  • Insulin Resistance*
  • Lipolysis* / drug effects
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Glucose Transporter Type 4
  • Insulin Receptor Substrate Proteins
  • Irs2 protein, mouse
  • Transcription Factors
  • Berberine
  • Proto-Oncogene Proteins c-akt
  • Glucose