Characters And Mechanism Of Glucose Transport During Acclimatization To Hypobaric Hypoxia

Characters and Mechanism of Glucose Transport during Acclimatization to Hypobaric HypoxiaIntroductionOxygen plays a major role in the energy metabolism of aerobic living organisms. Due to its low redox potential it serves as an electron acceptor in oxidation-reduction reactions which is necessary for the combustion of organic substrates such as glucose to yield energy in form of ATP. It is well known that the O2 efficiency of glucose oxidation is substantially higher than that of free fatty acids (FFA) oxidation. The ATP yield per O2 molecule is 25-60% higher with glucose than with FFA. Sherpa, high altitude resident, would be expected to get 25-60% more ATP per mol of O2 when burning carbohydrate than when buring FFA in their heart. Therefore, glucose is advantageous for anaerobic metabolism when O2 is limiting , because glucose can prime ATP production by anaerobic glycolysis. The initial step in the metabolism of glucose is its transport across the plasma membrane, a step that is "rate-limiting" in a vast majority of cells and tissues. Hence, control of glucose transport represents an important step in the action of a variety of hormones and other physiological stimuli that influence the cellular metabolism of glucose. Of particular importance is the role of stimulation of glucose transport in the adaptive response of cells and tissues to hypoxia. However, the acclimative change of potential ability to utilizing glucose during exposure to hypoxia and the mechnism was unkwown. Study on this can help to realize the nature and mechism of acclimatization or adaptation to high altitude. MethodsWistar rats were divided into four groups randomly: Control group (H0), hypoxic 5 days (H5), hypoxic 15 days (H15), hypoxic 30 days (H30). Animals of H5, 15, 30 group were exposed to hypobaric hypoxia chamber simulating 5000m high altitude for 5, 15, 30 days respectively, 23 hours per day. H0 group stayed outside of chamber. Arterial blood, skeletal muscle from hind leg, cerebral cortex were collected in the hypobaric hypoxic chamber. 3H-D-glucose was used to assay the glucose uptake rate (GUR) in skeletal muscle and cerebral cortex. The level of glucose, glycogen, phosphate creatine, ATP and lactate were assayed by enzyme methods. The intracellular and plasma membrane of skeletal muscle were separated by discontinuous sugar gradient (25, 35%). The maximal bind sites(Bmax) and Kd of glucose transporters and insulin receptor on themembrane were analysed by scatchard. The expression of protein and mRNA of GLUT1, GLUT4 of skeletal muscle membrane and GLUT3 of the cerebral cortex were detected by western blot and RT-PCR respectively. In another experiment, wistar rats were also divided into four groups: SS, SE, HS, HE. The rats in SS group stayed at seal level without swimming for 30 days. SE group stayed at seal level with swimming 1 hour/day, HS group was exposed to hypobaric hypoxia simulating 5000m high altitude for 30 days. The animals of HE group did swimming for one hour at chamber simulating 4000m high altitude, then were risen to 5000m. The blood gas, blood glucose and ATP, phosphate creatine, lactate, glucose, glycogen, the uptake rate of glucose and expression of mRNA of GLUT1,3,4 in skeletal muscle and cerebral cortex were determined by the same methods. The expression of GLUT1, 3, 4 were assayed by ELISA. ResultsIn skeletal muscle, there was no significant difference of content of ATP among H0, H5, H15, H30. In cerebral cortex, content of ATP of H5 was less than that of H0. There was no significant difference among H0, H15, H30. In skeletal muscle and cerebral cortex, the level of phosphate creatine and glycogen of H5, H15 reduced comparing with H0, but increased in H15, H30 compared with H5. Compared with H0, the glucose level of H5 in skeletal muscle and cerebral cortex didn't reduce significantly, but H15 and H30 increased. Blood glucose level of H5 reduced, then increased in H15, H30. The content of lactate of skeletal muscle and cerebral cortex increased in H5...