Our previous work, as well as that of others, indicates there is a post-receptor defect in the metabolism of glucose in severely burned or septic patients. It is our hypothesis that pyruvate dehydrogenase (PDH) is the site of the post-receptor defect. We therefore plan to explore the metabolic effect of stimulating PDH activity with dichloroacetate (DCA) in severely burned patients. We will assess the metabolic responses to DCA administration by means of stable isotopic tracers and mass spectrometry analyses. Because lactate is in rapid equilibrium with pyruvate, the balance between lactate oxidation and lactate release is a good indicator of PDH activity, and thus, the extent to which glucose is completely oxidized. We will therefore determine the effect of stimulation of PDH on lactate release, clearance, and oxidation in the basal state and during glucose infusion in severely burned patients. We will also quantify the changes in the rate of release of alanine, the rate of gluconeogenesis from lactate and alanine, and the rates of total glucose production and oxidation. These values will be related to changes in urea production. Furthermore, we will determine if stimulation of PDH activity will normalize the """"""""post-receptor"""""""" defect in insulin responsiveness, as determined by the euglycemic-hyperinsulinemic clamp technique The data obtained in burn patients will be compared with that collected in normal volunteers before and after seven days of bed rest in order to better assess the effect of burn injury, per se, on the metabolism of glucose.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK033952-05
Application #
3232375
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1983-12-01
Project End
1991-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
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