Date of Award

5-1995

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Human Ecology

Major Professor

Michael B. Zemel

Committee Members

Thomas C. Namey, David R. Bassett, Edward Howley, Paula Zemel

Abstract

(Part I.) The purpose of this study was to measure insulin regulated glucose transport and GLUT4 protein in aortic tissue from insulin-resistant vs. sensitive rats. We assessed basal and insulin-stimulated [3H]-2-deoxyglucose transport in aorta from lean vs. obese Zucker rats. In a muscle-bath system, insulin significantly stimulated aortic 2-deoxyglucose transport by 30% in lean and obese animals. Further, in the perfusion system with only luminal vessel exposed, insulin significantly stimulated 2-deoxyglucose transport in aorta of lean animals. Western blot analysis demonstrated that aorta contained substantial concentrations of GLUT4 protein. These data demonstrate that the aorta is insulin-sensitive and partially impaired in the insulin resistant animals. (Part II.) The purpose of this study was to determine if there is a fa allele effect in BN/fa rats subjected to a high fat diet. BN/BN and BN/fa male/female rats were fed 12% or 48% fat diets for 7 weeks. Food intake and weight change were recorded weekly to obtain an index of energy efficiency ratio (EER) and blood and tissue were harvested for subsequent analysis. Plasma insulin, glucose and cholesterol concentrations, perirenal and epididymal fat pad weights, EER, weight gain and food intake were all significantly higher in male rats on the 48% vs. 12% fat diet. BN/fa animals had heavier fat pads than BN/BN animals. The animals on the 48% fat diet had a significantly higher concentration of soleus GLUT4 protein vs. 12% fat diet. We have demonstrated that a high fat diet exacerbates insulin resistance and the aberrations associated with insulin resistance. The effects of the high fat diet are amplified in animals carrying one copy of the fa allele and female animals appear to be somewhat resistant to this diet-gene interaction. Additionally, we have demonstrated that a high fat diet increases the insulin responsive glucose transporter (GLUT4) protein in skeletal muscle. These data support the concept that syndrome X is a multifactorial syndrome that predominates in males, which is genetically determined and modulated by environmental influences.

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