Master of Science
Physiology and Biophysics
Dr. Roland Pittman
PO2 DEPENDENCE OF OXYGEN CONSUMPTION IN SKELETAL MUSCLE OF DIABETIC AND NON-DIABETIC RATS
By: Alexander C. Liles
A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at the Medical College of Virginia Campus, Virginia Commonwealth University
Virginia Commonwealth University, 2017
Advisor: Roland N. Pittman, Ph.D.
Department of Physiology and Biophysics
Type 2 diabetes mellitus (T2DM) is a major medical problem around the world, affecting nearly 6% of the world’s population. This study was an attempt to better understand physiological changes the disease may cause to the microcirculation and more specifically, to assess the dependence of oxygen consumption in skeletal muscle of a diabetic animal model. The spinotrapezius muscles of Goto-Kakizaki (G-K) and Wistar control rats were used to measure interstitial using phosphorescence quenching microscopy. The G-K rats spontaneously develop T2DM and serve as an appropriate model for the disease in humans. By rapidly arresting blood flow in the tissue and observing the resulting changes, an oxygen disappearance curve (ODC) was created. The ODC was used to calculate oxygen consumption rate (VO2) over the physiological range of PO2 values. The resulting VO2 vs PO2 curves were analyzed using Hill’s equation to fit the data and obtain values of several key parameters to quantitatively describe the PO2 dependence of oxygen consumption. When compared to healthy control rats, the G-K rats exhibited a significantly higher Vmax, or maximum rate of oxygen consumption, compared to the Wistar rats. The two rat sub-strains had similar values for P50, which indicates the PO2 at half maximal consumption. The overall higher maximal rate of consumption by the diseased animals could be explained by some disconnect in the consumption of oxygen by the mitochondria and the normal corresponding production of ATP. In conclusion, it was demonstrated that in situ muscle tissue from both diabetic and non-diabetic rats had a PO2 dependence of oxygen consumption over a wide range of PO2 values and the muscles of diabetic animals consumed oxygen at a higher maximal rate.
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