We have found that glycogen synthesis by rat hepatocytes is stimulated by amino acids, mercaptopicolinic acid and butyl-malonate. To investigate the mechanism of this stimulation, we will determine the effect of these agents on the concentration in hepatocytes of intermediates of the Krebs cycle of amino acids, phosphate esters and nucleotides. The distribution of these compounds between cytosol and mitochondria will be determined. Methods to measure these compounds at a picomole level by means of bacterial luciferase are being developed. Similar studies to compare hepatocytes from starved and fed streptozotocin diabetic rats will be developed. The effect of anoxia, oxygen tension, hormones (glucagon, insulin and epinephrine) on the acitve and total phosphorylase and on glycogen synthase in hepatocytes will be studied.