Jorge Calles-Escandon, M.D., (PI) is a graduate from the National University of Mexico who received training at Yale University and at the University of Vermont in metabolism and nutrition. He is strongly committed to nutrition research. His personal interest is the investigation of determinants of energy metabolism in man, using as models the closely related syndromes of obesity and Type II diabetes. This proposal will study the role of substrate cycles in regulation of energy metabolism, as well as their contribution to the distorted rates of energy metabolism of obesity and Type II diabetes. The underlying hypothesis is that either the magnitude and/or the regulation of substrate cycles will explain the absolute basal high rates of energy expenditure in the obese and diabetic states. We plan to measure substrate cycles for the glucose and lipid systems, involving thus 2 key insulin sensitive organs: the liver and the adipose tissue.l The project will encompass a comprehensive approach that will include state of the art techniques for: 1) energy metabolism (indirect calorimetry),k 2) tracer methodology (stable and radioactive isotopes) and, 3) physiological perturbations. Thermodynamically, substrate cycles operate at a low level in basal conditions, thus we will not limit our observations to the resting non- stimulated state but will also examine the response of the cycles under metabolic challenges: a) glucagon infusion,l b) epinephrine administration, and c) combination of glucagon and epinephrine. A detailed topographic characterization of our volunteers will let us define the importance of intra-abdominal fat as a correlate of distorted energy and fuel metabolism. This particular issue will help clarify discordant data in the literature regarding energy expenditure and metabolic abnormalities among obese patients. These studies will help to understand the basic mechanisms of the obese state and will provide insight into possible biochemical abnormalities that help explain the link between obesity and Type II diabetes. All the studies will be carried out at the Clinical Research Center of the University of Vermont. The Metabolic Unit is recognized as a leader group in obesity research. The environment is highly conductive to research, with interaction among the several members of the Unit as well as with close links with other departments. Techniques available include, among others, state of the art method to measure energy expenditure and the Biomedical Mass Spectrometry facility that enables the application of sophisticated stable isotope techniques to metabolic research in human beings.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK001963-04
Application #
3080886
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1990-04-01
Project End
1995-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Dvorak, R V; Calles-Escandon, J; Poehlman, E T (1998) Measurement and prediction of sympathetic nervous system activity in humans. Life Sci 62:1397-406
Arciero, P J; Smith, D L; Calles-Escandon, J (1998) Effects of short-term inactivity on glucose tolerance, energy expenditure, and blood flow in trained subjects. J Appl Physiol 84:1365-73
Toth, M J; Arciero, P J; Gardner, A W et al. (1996) Rates of free fatty acid appearance and fat oxidation in healthy younger and older men. J Appl Physiol 80:506-11
Calles-Escandon, J; Arciero, P J; Gardner, A W et al. (1995) Basal fat oxidation decreases with aging in women. J Appl Physiol 78:266-71
Calles-Escandon, J; Driscoll, P (1994) Free fatty acid metabolism in aerobically fit individuals. J Appl Physiol 77:2374-9
Copeland, K C; Nair, K S; Kaplowitz, P B et al. (1993) Discordant metabolic actions of insulin in extreme lipodystrophy of childhood. J Clin Endocrinol Metab 77:1240-5
Calles-Escandon, J; Horton, E S (1992) The thermogenic role of exercise in the treatment of morbid obesity: a critical evaluation. Am J Clin Nutr 55:533S-537S
Rothman, W C; Carrier, C; Mollen, N et al. (1989) RFrAP: a computer program for analysis of complex HLA RFLPs. Assignment of restriction fragments to haplotypes by segregation analysis. Hum Immunol 25:13-26