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DHEA EFFECT ON INSULIN RESISTENCE IN OBESE ZUCKER RATS. By : Victor Martinez. CONTENTS. Introduction DHEA Tumor Necrosis Factor Alpha (TNF) Insulin, NIDDM Rationale Methods Results Conclusions. DHEA. Most abundant circulating adrenal steroid
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DHEA EFFECT ON INSULIN RESISTENCE IN OBESE ZUCKER RATS By : Victor Martinez
CONTENTS • Introduction • DHEA • Tumor Necrosis Factor Alpha (TNF) • Insulin, NIDDM • Rationale • Methods • Results • Conclusions
DHEA • Most abundant circulating adrenal steroid • Beneficial for obesity, hyperlipidemia, diabetes, arteriosclerosis, and possibly insulin insensitivity • Precise biological function unknown • Precursor for testosterone and estrogen
TUMOR NECROSIS FACTOR (TNF) • Cytokine • Metabolic effects • Catabolic effect on fat cells • Effects fat metabolism, and regulates gene expression in fat tissue • Effects appetite, and G.I. tract function • Insulin antagonist • Promotes insulin insensitivity
INSULIN • Anabolic protein hormone • Secreted in times of excess nutrient availability • Promotes nutrient storage, and use of carbohydrates for energy • Directly related to serum glucose levels, and free fatty acids • Lipogenic at high levels
NIDDM • Exogenous insulin not needed to maintain life • Associated with decreased tissue response to insulin • 85% of sufferers are obese • Can be a result of insulin antagonist presence (TNF), cortisol, or GH
RATIONALE • To provide evidence that : • DHEA beneficial for obesity, insulin insensitivity,and GDR • Serum TNF levels would become lower in presence of DHEA
MATERIALS & METHODS • Animals : Female Zucker obese rats (FA/FA) 16 weeks old age matched with lean (FA/-) littermates (10 each) • Hyperinsulinemic-euglycemic clamp technique • Biochemical assays • TNF activity assays
RESULTS • Figure-1 • Figure-2 • Figure-3 • Figure-4
CONCLUSIONS • DHEA treatment reduced body weight, and serum TNF levels independently, and both may ameliorate insulin resistance in obese Zucker rats • Daily food intakes decreased in DHEA treated rats (60%) compared to control • Plasma insulin levels lowered significantly in DHEA rats compared to pair fed obese rats, and GDR increased significantly