Study On The Regulating Mechanism Of Glucose Metabolism Which HIF-2α Engages In Rat Livers Under Hypoxia Environment

Objective To explore the change of HIF-2α signal pathway in hepatic and the effect on blood glucose of rats under continuous hypoxia environment.Methods Sixty-four male Wistar rats were randomly divided into normoxia group(n=32)and hypoxia group(n=32).The normoxia group rats were fed in altitude 200 m area and hypoxia group rats were fed in high altitude(simulation 5000m)area,the eight rats from normoxia and hypoxia group were fasted 12 h and 50% glucose(2g/kg)were intraperitoneal injection to evalutate the glucose tolerance status of the rats at the one week,two weeks,three weeks and the four weeks,respectively.The next day,the rats were sacrificed and the livers were collected.The expression of HIF-2α,AKT,P-AKT,Gsk-3β,P-Gsk-3β were examined by Western Blotting.The PEPCK m RNA,G6 PC m RNA were measured by q RT-PCR.Results Compared with normoxia group,the weight,the fasting blood glucose and the area under the IPGTT blood glucose curve were significantly decreased(P <0.05).Compared with the normoxia group,the expression of HIF-2α was significantly higher in the hypoxia group(P<0.05),while P-AKT/AKT 、P-Gsk-3β/Gsk-3β ration were not significantly different between the normoxia and hypoxia group(P >0.05).Compared with the normoxia group,the levels of G6 PC m RNA was decreased significantly in the hypoxia group at one week and four weeks(P<0.05);the levels of PEPCK m RNA was significantly decreased in the hypoxia group at four weeks(P<0.05).Conclusions The expression of HIF-2α in hepatic were increased and blood glucose were decreased of rats under continuous hypoxia.Hypoxia induce HIF-2α expression to inhibite gluconeogenesis by decreasing the expression of G6 PC m RNA and PEPCK m RNA,and decrease blood glucose levels of rats.