In this program project the core is devoted to improving NMP spectroscopic methods needed in studies proposed by the three other projects on brain, kidney and liver/muscle. The core proposes to improve the necessary NMR localization methods and 1H and 13C spectroscopic methods and to improve the spectrometers performance. It also plans to evaluate the interpretation and quantitation of the NMR results. The brain will use 1H NMR and 1H observed 13C edit methods to measure catabolic fluxes from 1-13C glucose into cerebral pools of glutamate and in some cases lactate. The methods must be improved to obtain maximum sensitivity, resolution and accuracy. The results will then be interpreted quantitatively by evaluating the necessary parameters. In this way the brain project will be helped by the core to study human cerebral metabolism. One of the applications in the brain project of these methods will be to follow the turnover of 13C in lactate pools of stable stroke patients as a guide for therapy. Other directions to be studied in the brain will include time correlations in young adult phenylketonurics between blood and brain levels of phenylalanine. The kidney research will develop methods of quantitating and localizing 1H and 31P NMR spectra of the orthotopic human kidney. Time courses of changes in the osmolytes glycerophosphorocholine and betaine in response to changes in the state of hydration will be followed by 1H and 31P NMR. The NMR resonances will also be used to follow diabetes insipidus, acute renal failure and obstructive nephropathy in humans. 13C NMR measurements of glycogen synthesis and turnover. The roles of insulin/glucose/glucagon in the regulation of liver glycogen gluconeogenesis in humans by using 13C NMR to measure hepatic glycogenolysis in combination with 3 H glucose measurements of whole body glucose turnover rates.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK034576-06
Application #
3095353
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1990-09-20
Project End
1994-12-31
Budget Start
1991-02-07
Budget End
1991-12-31
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Hundal, Ripudaman S; Petersen, Kitt F; Mayerson, Adam B et al. (2002) Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. J Clin Invest 109:1321-6
Bischof, Martin G; Bernroider, Elisabeth; Krssak, Martin et al. (2002) Hepatic glycogen metabolism in type 1 diabetes after long-term near normoglycemia. Diabetes 51:49-54
Petersen, K F; Sullivan, J T (2001) Effects of a novel glucagon receptor antagonist (Bay 27-9955) on glucagon-stimulated glucose production in humans. Diabetologia 44:2018-24
Hyder, F; Phelps, E A; Wiggins, C J et al. (1997) ""Willed action"": a functional MRI study of the human prefrontal cortex during a sensorimotor task. Proc Natl Acad Sci U S A 94:6989-94
Phelps, E A; Hyder, F; Blamire, A M et al. (1997) FMRI of the prefrontal cortex during overt verbal fluency. Neuroreport 8:561-5
Dhankhar, A; Wexler, B E; Fulbright, R K et al. (1997) Functional magnetic resonance imaging assessment of the human brain auditory cortex response to increasing word presentation rates. J Neurophysiol 77:476-83
Jones, R P; Morris, G A; Waterton, J C (1997) The spatial dependence of spin-echo signals. J Magn Reson 124:291-7
Graham, G D; Kalvach, P; Blamire, A M et al. (1995) Clinical correlates of proton magnetic resonance spectroscopy findings after acute cerebral infarction. Stroke 26:225-9
Magnusson, I; Rothman, D L; Gerard, D P et al. (1995) Contribution of hepatic glycogenolysis to glucose production in humans in response to a physiological increase in plasma glucagon concentration. Diabetes 44:185-9
Rothman, D L; Magnusson, I; Cline, G et al. (1995) Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci U S A 92:983-7

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