Abstract
For the present thesis, the Zucker fatty rat was studied as a model of inherited obesity alongside the CoCl[2]-treated rat which represented a model of induced hyperlipaemia. Carbohydrate and lipid metabolism in these two rats were investigated. To elucidate the role of insulin and glucagon receptors in obesity and hyperlipaemia, liver and adipose tissue insulin and glucagon receptor-interactions were examined in freshly prepared liver and adipose tissue plasma membranes from these two rats and compared to their controls. In the Zucker fatty rat obesity was found to be associated with gross hypertriglyceridaemia and hyperinsulinaemia. The insulin resistance associated with this rat could be accounted for by a decrease in the number of insulin receptors at its target tissues examined in the present study. There was no alterations in the number or avidity of the glucagon receptors in the liver or adipose tissue of the Zucker fatty rat. Hypertriglyceridaemia of this rat was found to be associated with high activity of lipoprotein lipase. A mechanism for insulin resistance and another for hypertriglyceridaemia in this rat will be described in some detail. The polycythemia of the CoCl[2]-treated rat was found to be accompanied by moderate hypertriglyceridaemia compared to that of the Zucker fatty rat. The postulated glucagon resistance of the CoCl[2]-treated rat as well as for the Zucker rat was investigated in some detail. Glugacon basal level as well as after arginine stimulation was found to be within the normal range in the CoCl[2]-treated rats as set by their untreated controls. Furthermore, there was no abnormality detected in glucagon or insulin binding to liver or adipose tissue plasma membranes in these rats. The hypertriglyceridaemia of the CoCl2-treated rat was found to be due to a decrease in the plasma triglycerides removal rate. The role of cobalt in the aetiology of this induced hypertriglyceridaemia will be discussed in detail and a mechanism will be presented. Longitudinal studies in the effect of cobalt on rats was also investigated and results reported.