The Effect Of FGF-21on Glucose-metabolism In The Resistin-induced Insulin Resistance Liver Cells

With the improving of people’s living standard, diabetes gradually developed as a global disease that seriously impacts on human health. Type2diabetes mellitus is characterized by target-tissue resistance to insulin and connects with a variety of metabolic abnormalities. As an important blood glucose control organ, the liver is also the major organ of insulin resistance. The therapies for treatment of glucose metabolism disorders that caused by insulin resistance have been one of the main issues in diabetes studies. So far, the causing factors and the pathogenesis of insulin resistance is not very clear. Resistin is a cytokine that closely links with insulin resistance that was found by Steppan in2001. As reported, the hepatic glucose output is increased by promoting the expression of key enzymes of gluconeogenesis and glycogen decomposition after resistin treatment. Through this, the resistin can participate in the formation of hepatic insulin resistance and weaken the ability of insulin on the regulation of blood glucose. FGF-21is an important factor in glucose metabolism; its bioactivity is primarily detected in the liver. The liver cells, with insulin resistance caused by high concentrations of insulin, are able to make an effective response to FGF-21. The results show that resistin may be the potential drugs to solve the blood glucose imbalance caused by insulin resistance.In order to know the function of FGF-21in hepatic cells with insulin resistance induced by resistin over-expression, the model cells with insulin resistance were obtained caused by overexpression of resitin. In this study, HepG2cells were transfected with eukaryotic expression vector containing the human resistin gene, resistin expression the transfected cells was selected by Flow cytometry. The glucose uptake of the HepG2cells treated with different concentrations of insulin and FGF-21was detected by GOD-POD method. After being treated with FGF-21, the mRNA expression of GLUT1and PPAR-γ in the HepG2cells was detected by real-time-PCR, and the glycogen synthesis also detected by anthrone method.We successfully developed the model cell line (HepG2-R) which stably expressed human resistin. The glucose uptake by the cells was detected by the method of glucose oxidizes/peroxides (GOD-POD), the results showed that the sensitivity of the cell line to the insulin treatment significantly decreased. The model cell line became resistant to insulin, but FGF-21could effectively stimulate the glucose uptake by the model cell line in a dose-dependent manner. The mRNA expression of GLUT1was elevated in the cell line, and significantly increased after treatment by FGF-21. The expression of PPAR-y had no significant change. The results indicate that FGF-21could effectively regulate the GLUT1mRNA of the model cell line. The glycogen synthesis was tested by anthrone method. The glycogen synthesis in the model cell line was significantly lower than the control cells, but the glycogen synthesis in the model cell was effectively improved after treated with different concentrations of FGF-21.The experiment proved that FGF-21can promote cells for glucose consumption by stimulating glycogen synthesis.The cell line in which resistin is highly expressed has a reduced susceptibility to insulin. Although the high level of resistin makes cells insulin resistance, FGF-21can regulate the glycol-metabolism effectively in the cells.