Abstract

In this proposal We hypothesize that derangement's in carbohydrate metabolism of aging is associated with parallel changes in body composition. We plan to demonstrate these changes during the life span of rats, focusing mainly on muscle and hepatic glucose metabolism and intracellular pathways. We also hypothesize that caloric restriction may reverse many of the derangement's in glucose metabolism of aging rats.
Our Specific Aims are to study in aging rats: 1) The effects of body composition and plasma FFA concentration on insulin- and glucose-mediated glucose disposal, glycolysis, and glycogen synthesis. 2) The effects of body composition and plasma FFA concentration on in vivo hepatic glucose fluxes, glycogenolysis, gluconeogenesis. 3) The correlation between the specific alterations in in vivo hepatic and skeletal muscle glucose fluxes and the in vitro kinetics of the rate-determining enzymes of these metabolic pathways, such as glycogen synthase, glucokinase and glucose-6-phosphatase. 4) The impact of early intervention by caloric restriction on body composition and peripheral and hepatic glucose fluxes. Studies will be conducted in 2 rat models: Fischer 344 and Sprauge-Dawley, in 4 different age groups. The significance of this proposal is two fold. First it will quantify the role of increased fat mass on glucose metabolism in aging. Second, if not all impairment is fat mass related, it may point to the mechanisms that are true senescence.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AG000639-04
Application #
2516873
Study Section
Biological and Clinical Aging Review Committee (BCA)
Program Officer
Finkelstein, David B
Project Start
1994-09-01
Project End
1999-08-31
Budget Start
1997-09-30
Budget End
1998-08-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Albert Einstein College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Vuguin, P; Ma, X; Yang, X et al. (2001) Food deprivation limits insulin secretory capacity in postpubertal rats. Pediatr Res 49:468-73
Cases, J A; Gabriely, I; Ma, X H et al. (2001) Physiological increase in plasma leptin markedly inhibits insulin secretion in vivo. Diabetes 50:348-52
Barzilai, N; Gabriely, I (2001) The role of fat depletion in the biological benefits of caloric restriction. J Nutr 131:903S-906S
Gupta, G; She, L; Ma, X H et al. (2000) Aging does not contribute to the decline in insulin action on storage of muscle glycogen in rats. Am J Physiol Regul Integr Comp Physiol 278:R111-7
Cases, J A; Barzilai, N (2000) The regulation of body fat distribution and the modulation of insulin action. Int J Obes Relat Metab Disord 24 Suppl 4:S63-6
Barzilai, N; She, L; Liu, B Q et al. (1999) Surgical removal of visceral fat reverses hepatic insulin resistance. Diabetes 48:94-8
Barzilai, N; Gupta, G (1999) Revisiting the role of fat mass in the life extension induced by caloric restriction. J Gerontol A Biol Sci Med Sci 54:B89-96;discussion B97-8
Barzilai, N; Gupta, G (1999) Interaction between aging and syndrome X: new insights on the pathophysiology of fat distribution. Ann N Y Acad Sci 892:58-72
Barzilai, N; She, L; Liu, L et al. (1999) Decreased visceral adiposity accounts for leptin effect on hepatic but not peripheral insulin action. Am J Physiol 277:E291-8
Massillon, D; Barzilai, N; Hawkins, M et al. (1997) Induction of hepatic glucose-6-phosphatase gene expression by lipid infusion. Diabetes 46:153-7

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