The overall objective of this project is to study the regulation of glucose output by mammalian liver and kidney during neonatal development. The studies proposed will focus on four closely related areas: assessment of the mechanism of hormonal and enzymatic activation of initial glycogen mobilization in liver of the newborn, elucidation of the basis for the increased sensitivity of the hepatocyte with age to hormonal stimulation during neonatal growth, hormonal regulation of renal gluconeogenesis, and possible interaction between lipid oxidation and neonatal gluconeogenesis. Metabolic processes such as glycogenolysis, ketogenesis and gluconeogenesis will be measured in vivo, and in isolated hepatocytes or renal tubules in vitro. The basis for increased responsiveness of hepatocytes or renal tubules in vitro. The basis for increased responsiveness of hepatocytes with age to hormonal stimulation will be assessed by quantifying age-dependent changes in the number and/or affinity of alpha- and beta-adrenergic receptors on liver plasma membrane through binding experiments with specific radioligands and correlating the binding with glycogenolysis. The number of binding sites and/or affinity of ligands for receptors will be determined by Scatchard analysis of the binding data.
