The objective of this study is to investigate the development of hormonal and metabolic regulation of glycogen metabolism in rat liver. Specifically this will entail careful study of the last segment of gestation in the rat during which massive prenatal synthesis and accumulation of hepatic glycogen takes place, the neonatal period and attendant glycogenolysis, and the postnatal-to-weaning period of gradual development of adult patterns of regulation. In particular, the relationship between hepatic ultrastructure (i.e., endoplasmic reticulum) and key enzymes of glycogen synthesis and degradation will be monitored with regard to initial appearance, physiological relevance, and regulation. Of interest will be glycogen synthase and its corresponding phosphoprotein phosphatase activating enzyme synthase phosphatase. Methods of analysis will include those at the morphological level including electron microscopy, and the biochemical level including subcellular fractionation, enzyme localization, partial purification and analysis of catalytic and kinetic characteristics. Studies will also be directed toward understanding the question of prenatal and neonatal regulation of hepatic glycogen synthesis and degradation in offspring of rats made diabetic prior to mating. Such offspring frequently have problems at birth maintaining proper glycemia and are often dangerously hypoglycemic. This study will provide much new information regarding the specific question of development of regulation of hepatic glycogen metabolism, and the overall question of the ultrastructure and key enzymes of glycogen synthesis and degradation in effecting regulation of hepatic glycogen metabolisim.
