Glycogen Regulation in Isolated Perfused Near Term Monkey Liver

Abstract

ExtractGlycogen metabolism was studied in the isolated perfused liver of the monkey conceptus at 90% of gestation using an in situ recirculating perfusion system. Net uptake of glucose and galactose and the activities of the enzymes, glycogen synthetase and phosphorylase, were studied in response to varied perfusate composition. Synthetase activity was expressed as %I, the percentage of total synthetase activity in the active form. Perfusate glucose concentrations a s high as 700 mg/ 100 ml did not lead to net glucose uptake or to an increase in the baseline %I synthetase ( 4 1, mean & SEM). In the presence of 300 mg/100 ml glucose, insulin a t M increased %I to 8 i 2, and galactose > 75 mg/100 ml increased %I to 8 & 1. The combination of galactose, glucose, and insulin increased %I to 40 A 5. With this latter combination, synthetase activity was proportional to perfusate glucose concentration above 100 mg/100 ml. Phosphorylase activity was diminished by either galactose or insulin, and phosphorylase activity was lowest in the group receiving galactose, glucose, and insulin. Galactose was taken up by all livers, but net glucose uptake was not observed under any condition; net hexose uptake was observed in perfusions with galactose. Glycogen levels did not vary significantly with varied perfusate composition during the 30-min perfusion periods. Speculation W e speculate that galactose may be uniquely important for neonatal liver glycogen synthesis, and that its action is mediated through reciprocal changes in the activities of the enzymes, glycogen synthetase and phosphorylase. If liver glycogen is important for acute neonatal glucose homeostasis, then galactose may also be essential for maintaining circulating glucose concentration by ensuring glycogen synthesis during feeding.

Influence of Exogenous Glucagon on Fetal Glucose Metabolism and Ketone Production

“…The demonstration of increasing response to glucagon mJechon with advancing gestational age is also consistent with acute glucagon-stimulated glycogenolysis as liver glycogen content increases rapidly between 110 days and term in the fetal sheep (25). Enzymes necessary for glycogen synthesis as well as degradation are also present at this stage of gestation in the fetal sheep (3) as well as in other species (26). Increasing hepatic responsivity to glucagon, particularly with regard to hepatic adenyl cyclase activation (30) may also be important.…”

Galactose, Glucose, and Lactate Concentrations in the Portal Venous and Arterial Circulations of Newborn Lambs after Nursing

“…It has been well demonstrated that the fetal and neonatal liver can convert galactose to glycogen leading to net glycogen synthesis faster than they convert glucose to glycogen (19,20). The newborn liver converts galactose to glucose-1-phosphate faster in the suckling period than the adult period (21)(22)(23)(24)(25).…”

Sequential Intrahepatic Metabolic Effects of Enteric Galactose Alimentation in Newborn Rats

“…Previous investigations from our laboratory and other laboratories have demonstrated enhanced incorporation of galactose into glycogen when compared with glucose (2,3,6). Additional investigations have demonstrated that hepatic galactose uptake exceeds that for glucose in vitro, whereas activation of hepatic glycogen synthase and inactivation of glycogen phosphorylase was greater in the presence of galactose than that for glucose (5,6).…”

“…precursor for neonatal hepatic glycogen synthesis (2)(3)(4)(5)(6). Previous investigations from our laboratory and other laboratories have demonstrated enhanced incorporation of galactose into glycogen when compared with glucose (2,3,6).…”