Advantages of Hyperbaric Oxygen Treatment for Type 2 Diabetes Mellitus in Mice: Involvement of Leptin.

Background: Hyperbaric oxygen treatment (HBOT) is clinically used to improve oxygen supply to hypoperfused tissues under certain conditions. HBOT can decrease the incidence of autoimmune diabetes in nonobese diabetic mice by reducing apoptosis and increasing β-cell proliferation. HBOT ameliorates glucose tolerance in Type 2 diabetes (T2D) mellitus patients, but the underlying mechanism needs further investigation. Methods: We used a diet-induced T2D mouse model and a genetic mouse model (ob/ob mice) to evaluate the effects of HBOT on serum glucose levels in mice. The body weights and blood glucose levels of the mice were measured weekly. An oral glucose tolerance test (OGTT) was performed 12 weeks after the start of the experiment. All the mice were euthanized, and the serum and liver tissues were collected to test the total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, malondialdehyde, and antioxidant enzymes. Results: Our results demonstrated that HBOT can delay/attenuate the onset of diet-associated T2D in wild-type mice. However, HBOT had no significant effects on blood glucose or T2D incidence in ob/ob mice. Furthermore, we found that HBOT improved glucose tolerance and liver steatosis in diet-induced T2D model mice but not in ob/ob mice. Our results indicated that the effects of HBOT on T2D were dependent at least partly on the presence of leptin. Conclusion: Our study offers a rationale for using serum leptin as a predictor of clinical outcomes of HBOT and elucidates possible reasons why many patients may experience HBOT failure.