| Hyperbaric oxygen(HBO)therapy as a new non-invasive scientific treatment can ameliorate the symptoms such as ischemia and hypoxia.Researcher show that hypoxia can induce insulin resistance.Type 2 diabetes millitus(T2DM),which is mainly characterized by insulin resistance,has become an urgent problem in the world today.The number of T2 DM patients is increased every year.The plasma level of nesfatin-1,the newly found brain-gut peptide,is inversely related to insulin resistance.Previous studies also indicate that it can promote glucose utilization to reduce blood glucose level.Objectives: To investigate whether hyperbaric oxygen could improve insulin resistance,then activating the insulin-dependent Akt signaling pathway to promote the expression of glucose transporter 4(GLUT4)in skeletal muscle and the phosphorylation of AMP-activated protein kinase(AMPK)to improve glucose uptake and utilization and thereby lower blood glucose,and to investigate whether hyperbaric oxygen can change the plasma levels of nesfatin-1 and leptin.Methods: Five-week-old male C57BL/6J mice were fed with a high fat diet(HFD)for one week.Streptozotocin(60mg/kg)was injected intraperitoneally for next three days,Then the high-fat diet was continued to induce type 2 diabetic model.Age-matched mice were fed with simple high-fat diet as control.The high-fat diet mice and type 2 diabetic mice were respectively divided into normobaric normoxic groups and hyperbaric oxygen treatment groups(HFD group,HFD + HBO group,T2 DM group,T2 DM + HBO group).The hyperbaric oxygen treatment group was given 2 ATA 100% oxygen for 1 hour per day for one week.The changes of fasting blood glucose,insulin resistance index and food intake were observed.Glucose tolerance test and insulin tolerance test assess glucose metabolism in mice.Immunofluorescent histochemical techniques were used to detect the expression of NPY in the hypothalamic arcuate nucleus(Arc)and GLUT4 in skeletal muscle.Hematoxylin-eosin(HE)staining was used to observe the brown adipose tissue morphology.Akt and AMPK phosphorylation in skeletal muscle was detected by western blot.Uncoupling protein-1(UCP1)expression level in brown adipose tissue was also measured.ELISA kits were used to measure nesfatin-1 and leptin levels.Results: The rate of successful type 2 diabetic model creation was about 70% with impaired glucose tolerance and insulin resistance.(1)Hyperbaric oxygen can significantly reduce the blood glucose level of type 2 diabetic mice(T2DM+HBO vs.T2DM:(-1.16 ±2.57)mmol/L vs.(7.50 ± 4.37)mmol / L,P < 0.01),but there was no significant difference in body weight gain((0.80 ± 0.62)g vs.(0.72 ± 0.54)g,P > 0.05).Body weight gain of HFD mice treated with hyperbaric oxygen treatment increased significantly(HFD+HBO vs.HFD:(0.77 ± 0.81)g vs.(2.56 ± 1.11)g,P < 0.01),mainly due to the proportion of white fat(inguinal fat,epididymal fat and perirenal fat)in body weight was significantly increased after hyperbaric oxygen treatment(5.77% ± 1.38% vs.4.13% ± 1.27%,P < 0.05);(2)Hyperbaric oxygen activated the NPY-positive neurons in arcuate nucleus(Arc)of type 2diabetic mice(466 ± 131.52 vs.298 ± 35.35,P < 0.05)and the amount of 12 h accumulated food intake was significantly increased((6.76 ± 0.61)g vs.(5.02 ± 1.19)g,P < 0.05);(3)Hyperbaric oxygen ameliorated insulin resistance(HOMA-IR: 31.98 ± 11.05 vs.45.33 ±12.81,P < 0.05)in type 2 diabetic mice;(4)Hyperbaric oxygen treatment increased the expression of GLUT4 and the level of phosphorylated Akt(p-Akt)in skeletal muscle of type2 diabetic mice,then promoting myocyte to uptake glucose.Hyperbaric oxygen also stimulated increased AMPK phosphorylation(p-AMPK)levels in muscle both in T2 DM and HFD mice;(5)Although there is no significant difference in the ratio of brown fat(HFD+HBO vs.HFD: 0.18% ± 0.05% vs.0.21% ± 0.03%,P > 0.05;T2DM+HBO vs.T2DM:0.23% ± 0.06% vs.0.23% ± 0.05%,P > 0.05)between groups,the morphological staining of BAT showed that hyperbaric oxygen could increase the number of brown adipocytes per unit of vision in type 2 diabetic mice(883 ± 157.02 vs.558.87 ± 51.87,P < 0.05)and increase the expression of UCP1,that indicated that hyperbaric oxygen may promote energy expenditure;(6)The level of plasma nesfatin-1(HFD+HBO vs.HFD:(691.82 ± 102.98)pg/m L vs.(451.86 ± 120.44)pg/m L,P > 0.05;T2DM+HBO vs.T2DM:(491.62 ± 52.42)pg/m L vs.(614.29 ± 85.28)pg/mL,P > 0.05)and leptin(HFD+HBO vs.HFD:(1.65 ± 0.29)ng/m L vs.(1.78 ± 0.10)ng/mL,P > 0.05;T2DM+HBO vs.T2DM:(1.82 ± 0.14)ng/m L vs.(1.83 ± 0.13)ng/m L,P > 0.05)were with no significant change.Conclusion: The results showed that hyperbaric oxygen improved the insulin resistance of type 2 diabetic mice,activating the Akt signaling pathway,increasing the expression of GLUT4 in skeletal muscle to promote glucose uptake.Hyperbaric oxygen also increased energy by increasing the expression of UCP1 in brown fat tissue.It provides a theoretical basis for the treatment of type 2 diabetes by hyperbaric oxygen,expanding the application of hyperbaric oxygen in metabolism. |
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