In most species, increased endogenous production of glucocorticoids (Cushing's syndrome), or elevated glucocorticoids from an exogenous source, produce metabolic alterations similar to those which characterize the type-2 diabetes of man. The prominent disturbances seen in most species with elevated corticoid levels are hyperphagia, obesity, hyperinsulinemia, abnormal glucoregulation and glucose intolerance. Genetic models of obesity such as the Zucker fa/fa rat and ob/ob mouse share many of these same disturbances, and are known to be dependent on both elevated insulin levels and some level of glucocorticoid production for the full expression of the disorder. Four separate experimental approaches focussing on the roles of insulin and corticosterone will be used. In the initial series of studies, the doses, patterns and sites of administration of corticosterone sufficient to produce Cushing's syndrome in intact Sprague-Dawley as well as heterozygote and homozygote lean Zucker rats will be determined. The second series of studies will examine several potential mechanisms to account for reports of differences in the effectiveness of corticotropin to produce Cushing's-like syndromes in some strains of laboratory rats. In a third series of studies the interactions between corticotropin, corticosterone and insulin on the induction of hyperphagia, diabetes and obesity will be examined. Finally, the fourth series of studies will determine the role of the CNS in mediating the metabolic and growth effects of corticosterone. The results of these studies will detail the sufficient conditions for establishing an obese hyperglycemic syndrome in Sprague-Dawley rats that is similar in all aspects to that expressed in animals having a genetic basis of obesity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK042446-03
Application #
2142280
Study Section
Biopsychology Study Section (BPO)
Project Start
1991-09-20
Project End
1995-08-31
Budget Start
1993-09-01
Budget End
1995-08-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Maryland College Park
Department
Nutrition
Type
Other Domestic Higher Education
DUNS #
City
College Park
State
MD
Country
United States
Zip Code
20742
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