This study is designed to investigate the biochemical mechanisms involved in the regulation of hepatic carbohydrate metabolism by insulin, catecholamines, glucagon and vasopressin. Emphasis will be placed on the regulation of glycogen synthesis and degradation by these hormones using isolated liver cells. Glycogen synthase and phosphorylase, along with their phosphatases and kinases will be measured. Currently cyclic AMP and Ca 2 ion are being emphasized as regulators of these enzymes. However, studies in our laboratory and elsewhere indicate that while glucagon may act through a cyclic AMP dependent mechanism, this is clearly not the case for vasopressin or alpha-effects of catecholamines. While vasopressin acts through a mechanism which is dependent on the presence of extracellular Ca ions phenylephrine is much less dependent on the presence of Ca. The proposed project is designed to investigate the cyclic AMP independent mechanisms by which insulin, vasopressin and alpha-catecholamines regulate hepatic carbohydrate metabolism. Emphasis will be placed on the possible role of phospholipid turnover and lysosomes in hormone action.