Free fatty acid-induced insulin resistance and its mechanism in HepG2 cell

Objective To explore free fatty acid-induced insulin resistance and its molecular mechanism in HepG2 cell.Methods HepG2 cells were incubated in DMEM medium with palmitate(0.25mmol/L) or insulin(100nmol/L) before the cells were stimulated with 100nmol/L insulin.Glucose concentration in medium,glycogen contents and protein level of IRS-2 were measured,(respectively) before and after adding wortmannin(PI3K inhibitor).(Results)In palmitate and insulin treatment groups,glucose concentration was significantly increased(P0.05), glycogen contents and protein level of IRS-2 were significantly decreased compared with those in control group(P0.01).Before and after wortmannin intervention,protein level of(IRS-2) was not significantly different in palmitate group(P0.05),which was markedly different in normal group(P0.01).Conclusion(After) HepG2 cells were incubated with palmitate,glucose metablism,gluconeogenesis,glycogenesis and glycogenlysis were affected by palmitate.Insulin resistance was induced because of the impairment of insulin receptor singling.Defects of IRS-2 and some PI3K-associated molecules might be responsible for the occurence of free fatty acid-induced insulin resistance.