Methods will be developed and applied to the quantitation of pathways of carbohydrate and lipid metabolism. Using a split monkey brain preparation, an effect of insulin on glucose metabolism by the hypothalamus will be sought. From the fate of C14 of specifically C14-labeled fatty acids, the extent that alpha- and omega- oxidation contribute to fatty acid metabolism will be determined in muscle, liver, and brain during starvation and diabetes mellitus. The fate of the carbons of ketone bodies in these tissues will also be assessed including their possible contribution of intermediates for gluconeogenesis. Yields of C14O2 from specifically labeled fatty acids will be used as a measure of formation of free intermediates in fatty acid oxidation. The source of fructose in placenta will be measured by tracing its formation from C14- and H3-labeled glucose. For this the stereospecificity of the enzymes of the polyol pathway in regard to reduced nucleotide formation will be determined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK014507-18
Application #
3225231
Study Section
Metabolism Study Section (MET)
Project Start
1978-05-01
Project End
1988-04-30
Budget Start
1987-05-01
Budget End
1988-04-30
Support Year
18
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Bederman, Ilya R; Chandramouli, Visvanathan; Sandlers, Yana et al. (2013) Time course of hepatic gluconeogenesis during hindlimb suspension unloading. Exp Physiol 98:278-89
Basu, Rita; Chandramouli, Visvanthan; Schumann, William et al. (2009) Additional evidence that transaldolase exchange, isotope discrimination during the triose-isomerase reaction, or both occur in humans: effects of type 2 diabetes. Diabetes 58:1539-43
Spring-Robinson, Chandra; Chandramouli, Visvanathan; Schumann, William C et al. (2009) Uptake of 18F-labeled 6-fluoro-6-deoxy-D-glucose by skeletal muscle is responsive to insulin stimulation. J Nucl Med 50:912-9
Basu, R; Basu, A; Chandramouli, V et al. (2008) Effects of pioglitazone and metformin on NEFA-induced insulin resistance in type 2 diabetes. Diabetologia 51:2031-40
Basu, Rita; Chandramouli, Visvanathan; Dicke, Betty et al. (2008) Plasma C5 glucose-to-2H2O ratio does not provide an accurate assessment of gluconeogenesis during hyperinsulinemic-euglycemic clamps in either nondiabetic or diabetic humans. Diabetes 57:1800-4
Burgess, Shawn C; Chandramouli, Visvanathan; Browning, Jeffrey D et al. (2008) Complicating factors in the application of the ""average method"" for determining the contribution of gluconeogenesis. J Appl Physiol 104:1852-3;author reply 1854-5
Bock, Gerlies; Schumann, William C; Basu, Rita et al. (2008) Evidence that processes other than gluconeogenesis may influence the ratio of deuterium on the fifth and third carbons of glucose: implications for the use of 2H2O to measure gluconeogenesis in humans. Diabetes 57:50-5
Basu, Rita; Shah, Pankaj; Basu, Ananda et al. (2008) Comparison of the effects of pioglitazone and metformin on hepatic and extra-hepatic insulin action in people with type 2 diabetes. Diabetes 57:24-31
Weickert, Martin O; Loeffelholz, Christian V; Roden, Michael et al. (2007) A Thr94Ala mutation in human liver fatty acid-binding protein contributes to reduced hepatic glycogenolysis and blunted elevation of plasma glucose levels in lipid-exposed subjects. Am J Physiol Endocrinol Metab 293:E1078-84
Bock, Gerlies; Chittilapilly, Elizabeth; Basu, Rita et al. (2007) Contribution of hepatic and extrahepatic insulin resistance to the pathogenesis of impaired fasting glucose: role of increased rates of gluconeogenesis. Diabetes 56:1703-11

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