Research On The Role And Related Mechanisms By HGF/C-Met System On Improving Insulin Resistance

Obejective:To explore the effects of hepatocyte growth factor on insulin resistance(IR) in high-fat diet fed C57BL/6 male mice and its possible mechanisms.Methods:18 C57BL/6 male mices (19-21g) were induced to be insulin resistant models by being randomly grouped into normal diet group (NC), high-fat diet group 1 (HFD1), and high-fat diet group 2 (HFD2),all the six mices in each group. During 12 weeks of the treatment, body weight,food intakes,fast glucoses were detected at week 10,11 and 12, and post chanllage blood glucose levels with area under the curve of blood glucose (AUC of blood glucose) were also calculated at week 12.Started from week 12, HFD1 group were intraperitoneally injected saline for 4 weeks, HFD2 group were intraperitoneally injected HGF for 4 weeks,these mices were continued on high-fat diet fed.After 4 weeks of the treatment, the mice were fasted for 12h hours and weighed before sacrificed. Collected blood specimens and liver tissue samples to move on to the next step.The level of fasting blood glucose (FBS), fasting insulin (FINS), then HOMA-IR and ISI were also calculated. Serum alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Triglyceride (TG), Total Cholesterol (TC), Low density lipoprotein (LDL), High density lipoprotein (HDL), Free fatty acids (FFAs) were also measured.The liver was dissociated and weighed, then Liver index was calculated. The liver tissues were prepared into 10% liver homogenate for measuring the levels of liver TG and TC.Results:In the aspect of glucose tolerance and blood glucose level comparcd with HFD1 group, HGF group had a lower blood glucose and smaller AUC of blood glucose (p<0.05) and lower serum insulin (p<0.05).At the same time, HGF group had lower HOMA-IR and higher ISI than HFD1 group.In aspect of lipids, HGF group had lower serum TG,Tc and LDL level than HFDl group(p<0.05),and different decreased extent of FFA with different increased HDL. In aspect of liver function, HGF group had a significantly lower serum level of ALT,ALT than HFD1 group (p<0.05). In aspect of liver weight and liver index, HGF group had a lower liver weight,but liver index doesn’t has any difference.On the level of liver TG and liver TC, there is also a decreased trend in HGF group(p<0.05).Conclusion:The C57BL/6 mice IR model was successfully established by feeding high-fat diet for 12 weeks. This model metabolic characteristic was coupled with hyperlipidemia. Firstly, HGF can correct abnormal glucose tolerance of IR mice,decrease level of insulin,improve the insulin sensitivity,these phenomenons indicate that HGF could improve IR though regulating glucose mctabolism.and the specific mechanism still be needed further study. Secondly, HGF can decrease liver weight and liver TG and liver TC;HGF also can decrease the serum level of ALT,AST,TG,Tc and LDL, increase the serum level of HDL, these phenomenons show that HGF improve liver function,decrease the extent of liver steatosis significantly, improve IR by correcting lipid metabolism disorder.