Malonyl-CoA Exacerbates High Glucose-Induced Insulin Resistance in IR-HepG2 Cells by Inhibiting the PI3K/Akt Pathway
ZHANG Xin1, ZHANG Feng1,2*
This study explores the potential mechanism of the effect of malonyl-CoA on insulin resistance in high glucose-induced IR-HepG2 (insulin resistance HepG2) cells. The insulin resistance model of HepG2 cells was induced by high glucose combined with a high concentration of insulin, and interventions were carried out with different concentrations of malonyl-CoA (0 μmol/L, 20 μmol/L, 50 μmol/L, 100 μmol/L). This study evaluated glucose consumption, glucose uptake, fatty acid metabolism changes, and apoptosis of IR-HepG2 cells. The expression of proteins related to insulin resistance, such as the PI3K/Akt pathway, AMPKα/p-AMPKα protein, and the apoptosis-related protein Bcl-2, was detected by Western blot. The results showed that malonyl-CoA intervention significantly reduced glucose consumption (P<0.000 1) and glucose uptake (P<0.01) in IR-HepG2 cells, promoted the accumulation of cellular TG (triglyceride) (P<0.05), and led to disorders of glucose and lipid metabolism in IR--HepG2 cells. At the molecular mechanism level, malonyl-CoA intervention could increase the level of protein Kmal (lysine malonylation) in IR-HepG2 cells, downregulate the expression of AMPKα protein and p-AMPKα, and inhibit the PI3K/Akt signaling pathway; inhibit the expression of the anti-apoptotic protein Bcl-2 (P<0.01), and promote cell apoptosis, thereby exacerbating insulin resistance in IR-HepG2 cells. In conclusion, malonyl-CoA can cause disorders of glucose and lipid metabolism in IR-HepG2 cells, affect cell apoptosis, increase the level of protein Kmal, inhibit the PI3K/Akt pathway, and induce cell apoptosis, thus exacerbating IR-HepG2 cells insulin resistance.
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