Hypertension and diabetes mellitus are major health problems that often co-exist in the African-American population. Persistent hypertension triples the incidence of heart disease and stroke and magnifies the adverse effects of diabetes. Yet, the effects of diabetes in hypertensive individuals are not well studied. Further, there is very little data available on the contribution of androgens to, or the effects of estrogen treatment on, cardiovascular function in diabetic men or rats. This research training plan is designed to give me a firm foundation in experimental physiology and the interpretation of complex data.
My specific aims for the project period are to test the hypotheses that: A. The effects of insulin depletion on blood pressure and sexual function will be greater in middle-aged hypertensive male rats than in middle-aged """"""""normotensive""""""""male rats. Further, the effects of insulin depletion will be greater in middle-aged than in younger male rats. B. The effects of insulin depletion in male rats will include reduced hypothalamic sympathoinhibition. C. The effects of insulin depletion in male rats are modified by the gonadal steroid milieu. Thus, depletion of testosterone is associated with greater insulin resistance. Further, any beneficial effects of estrogen treatment in diabetic male rats will be greater in intact or testosterone-replaced males than in testosterone-depleted (castrated) males.
|Hamblin, Milton; Smith, Holly M; Hill, Michael F (2007) Dietary supplementation with vitamin E ameliorates cardiac failure in type I diabetic cardiomyopathy by suppressing myocardial generation of 8-iso-prostaglandin F2alpha and oxidized glutathione. J Card Fail 13:884-92|
|Hamblin, Milton; Friedman, David B; Hill, Salisha et al. (2007) Alterations in the diabetic myocardial proteome coupled with increased myocardial oxidative stress underlies diabetic cardiomyopathy. J Mol Cell Cardiol 42:884-95|
|Smith, Holly M; Hamblin, Milton; Hill, Michael F (2005) Greater propensity of diabetic myocardium for oxidative stress after myocardial infarction is associated with the development of heart failure. J Mol Cell Cardiol 39:657-65|