Monitoring of Energy Metabolism by Organic Acid Profiling Analysis in Plasma of Type 2 Diabetic Mice

Abstract

Objective:: This study was conducted to investigate energy metabolism based on changes in organic acids in diabetes and to establish a correlation between metabolites or bone microarchitecture and the glucose index in type 2 diabetic mice. Method:: Seven-week-old male C57BL/6 mice were randomly divided into a non-diabetic group and a diabetic group. The diabetic group was fed a high-fat diet (HFD) that induced insulin resistance for 5 weeks. Afterwards, diabetes was induced by a single streptozotocin injection. Both the groups were fed a normal diet and HFD diet for 9 weeks. Results:: The fasting blood glucose level glycosylated hemoglobin (HbA1c) significantly increased in diabetic mice. Bone-alkaline phosphatase activity decreased in the diabetic group. Diabetes increased the levels of ketone bodies, including 3-hydroxybutyric, acetoacetic and butyric acid, whereas it decreased Krebs cycle components, including succinic acid and malic acid, as well as levels of glycolytic products, including lactic acid. Diabetes also induced a shortage of trabecular bone mineral density (BMD) by the regulation of trabecular morphometric parameters in the femur and tibia. Correlation analysis indicated that BMD, Krebs cycle components and lactic acid levels were negatively correlated with HbA1c, whereas ketone bodies were positively correlated with HbA1c. Conclusion: : This research suggested that uncontrolled HbA1c can affect bone loss, production of ketone bodies and utilization of glucose metabolites for energy production in type 2 diabetes.