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 #
5R01DK042446-02
Application #
3243519
Study Section
Biopsychology Study Section (BPO)
Project Start
1991-09-20
Project End
1994-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Maryland College Park
Department
Type
Other Domestic Higher Education
DUNS #
City
College Park
State
MD
Country
United States
Zip Code
20742
Edens, N K; Moshirfar, A; Potter, G M et al. (1999) Adrenalectomy reduces adiposity by decreasing food efficiency, not direct effects on white adipose tissue. Obes Res 7:395-401
Trocki, O; Baer, D J; Castonguay, T W (1995) An evaluation of the use of total body electrical conductivity for the estimation of body composition in adult rats: effect of dietary obesity and adrenalectomy. Physiol Behav 57:765-72
Trocki, O; Baer, D J; Castonguay, T W (1995) Comparison of effects of adrenalectomy and RU-486 in rats given a choice of maintenance diet and fat supplement. Am J Physiol 269:R708-19
Hamelink, C R; Currie, P J; Chambers, J W et al. (1994) Corticosterone-responsive and -unresponsive metabolic characteristics of adrenalectomized rats. Am J Physiol 267:R799-804
Bligh, M E; Bhagwat, S A; Castonguay, T W (1993) Aldosterone diurnal rhythm in the rat: a question of cross-reactivity? Physiol Behav 53:845-8
Kramlik, S K; Altemus, M; Castonguay, T W (1993) The effects of the acute administration of RU 486 on dietary fat preference in fasted lean and obese men. Physiol Behav 54:717-24
Bligh-Tynan, M E; Bhagwat, S A; Castonguay, T W (1993) The effects of chronic cold exposure on diurnal corticosterone and aldosterone rhythms in Sprague-Dawley rats. Physiol Behav 54:363-7
Bligh, M E; Douglass, L W; Castonguay, T W (1993) Corticosterone modulation of dietary selection patterns. Physiol Behav 53:975-82
Kamara, K S; Kamara, A K; Castonguay, T W (1992) A reexamination of the effects of intracerebroventricular glucocorticoids in adrenalectomized rats. Brain Res Bull 29:355-8