Through the use of (1) binding studies with purified hepatocyte membranes (2) liver perfusion studies with the isolated organ and (3) whole animal studies, the proposed investigation seeks to examine the interaction of the glucoregulatory hormones: insulin and glucagon, and the lipoproteins VLDL, IDL and HDL. The binding studies will concentrate on a potential interaction at the membrane bound receptor level. The perfusion studies will examine uptake and catabolism of lipoproteins by the liver under the influence or lack of insulin and glucagon and conversely, check potential lipoprotein influence on insulin and glucagon extraction. Glucose removal and production by the perfused liver will also be examined to see if lipoprotein-hormonal interaction can influence these processes. Finally, animals will be treated with 4 amino pyrazolopyrimidine to reduce lipoprotein levels, after which labelled glucose will be introduced via duodenal catheter. Glucose extraction will be measured and the influence of supplemental lipoproteins assessed. This work addresses potential links between diabetes and heart disease by proposing an interactive role for glucoregulatory hormones and lipoproteins. It may also serve to elucidate glucose handling by the liver in Maturity Onset Diabetes and possibly reveal some relationships fundamental to insulin and glucose homeostasis.
