Abstract
Background: The objectives of the present study are to investigate whether cajanonic acid A (CAA) can reduce insulin resistance (IR) in HepG2 cells and to gain a preliminary understanding of the mechanisms underlying this effect.Methods: Following induction of IR in HepG2 cells, we tested the regulatory effect of CAA on glucose consumption and evaluated hepatocyte production of IL-6, TGF-β, and key molecules in the insulin transduction pathway. A transwell co-culturing system was used to assess the effect of CAA on IR in HepG2 cells during the differentiation of CD4+ T cells by calculating the ratio of (Th17)/regulatory T cell (Treg). We evaluated the effect of CAA on the expression of IL-17RC cells and HepG2 cell apoptosis by immunofluorescence and flow cytometry assay.Results: CAA improved dexamethasone-induced reduction in glucose consumption in HepG2 cells, inhibited hepatocyte production of IL-6 and TGF-β, increased the expression of IL-17RC cell, and increased cellular apoptosis in insulin-resistant HepG2 cells. When co-cultured with CD4+ T cells, insulin-resistant HepG2 cells induced a decrease in the ratio of Th17/Treg, but CAA dampened the effect. Application of IL-6 and TGF-β, together with CAA, reversed the effect of CAA on insulin-resistant HepG2 cells. Overexpression of IL17R, however, counteracted the effect of IL-6 neutralizing antibody within the culture system.Conclusion: CAA can regulate the ratio of Th17/Treg by mediating the expression of IL-6 and TGF-β in insulin-resistant HepG2 cells.
Highlights
Insulin resistance (IR) is critical in the development of type 2 diabetes mellitus (T2DM) [1], which is characterized by reduced responsiveness of cells to normal circulating concentrations of insulin
Using an established cell model of insulin resistance (IR), we evaluated the effect of cajanonic acid A (CAA) on regulation of IR
We found that CAA could improve dexamethasone-induced IR in HepG2 cells, promoted hepatocyte production of IL-6 and suppressed hepatocyte production of TGF-β, increased expression of IL-17RC, and increased cell apoptosis in insulin-resistant HepG2 cell
Summary
Insulin resistance (IR) is critical in the development of type 2 diabetes mellitus (T2DM) [1], which is characterized by reduced responsiveness of cells to normal circulating concentrations of insulin. In vitro studies in HepG2 cells revealed that IR in HepG2 cells is mainly associated with deficient glycogenesis, impaired hepatic glucose production and dysfunction of the insulin signal transduction pathway [3,4]. Methods: Following induction of IR in HepG2 cells, we tested the regulatory effect of CAA on glucose consumption and evaluated hepatocyte production of IL-6, TGF-β, and key molecules in the insulin transduction pathway. Results: CAA improved dexamethasone-induced reduction in glucose consumption in HepG2 cells, inhibited hepatocyte production of IL-6 and TGF-β, increased the expression of IL-17RC cell, and increased cellular apoptosis in insulin-resistant HepG2 cells. When co-cultured with CD4+ T cells, insulin-resistant HepG2 cells induced a decrease in the ratio of Th17/Treg, but CAA dampened the effect. Conclusion: CAA can regulate the ratio of Th17/Treg by mediating the expression of IL-6 and TGF-β in insulin-resistant HepG2 cells
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