1133-P: Four Days of Hyperoxia Exposure Confers Sustained Improvement in Glucose Homeostasis

Abstract

Obesity and type 2 diabetes are co-morbidities, and their prevalence is continually growing. In obesity, in the face of lipid accumulation, adipose tissue become hypoxic with reduced blood flow, accompanied by low grade inflammation and insulin resistance. We therefore hypothesized that exposure to high oxygen (hyperoxia) could improve glucose homeostasis in obesity. We treated normal and fast-food diet (40% fat)-induced obese mice (10 months old) with hyperoxia (95%) for 4 days and quantified the effects on glucose homeostasis and insulin sensitivity. We found that immediately after the hyperoxic treatment, glycemia was modestly higher compared to pretreatment levels. However, both fasting and post-challenge blood glucose levels were significantly decreased after 6 days of hyperoxia treatment in both normal (28±8%; p=0.01) and obese mice (36±4%; p=0.007)). Plasma insulin levels decreased by 41% in both normal (p=0.0026) and obese (p=0.0033) mice and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) values were also significantly decreased (63±4%; p=0.0009 in normal and 55±13%; p=0.0049 in obese mice)after hyperoxia treatment, indicating that the improvements in glucose homeostasis were associated with improved insulin sensitivity. Surprisingly, these metabolic improvements were maintained more than one month after hyperoxia treatment, and occurred without significant effects on weight. These results demonstrate that exposure to hyperoxia improves fasting blood glucose levels, glucose tolerance and insulin sensitivity, suggesting that the hyperoxia treatment may provide a new approach for supportive treatment of diabetes and obesity. Disclosure S. Jain: None. A.V. Harrison: None. F. Lorenzo: None. D. McClain: None. Funding U.S. Department of Veterans Affairs; National Institute of Diabetes and Digestive and Kidney Diseases