Simultaneous synthesis and degradation of rat liver glycogen. An in vivo nuclear magnetic resonance spectroscopic study.

Abstract

Using "3C nuclear magnetic resonance spectroscopic methods we examined in vivo the synthesis of liver glycogen during the infusion of D-11-13Cjglucose and the turnover of labeled glycogen during subsequent infusion of D-11-13Cjglucose. In fasted rats the processes of glycogen synthesis and degradation were observed to occur simultaneously with the rate of synthesis > degradation leading to net glycogen synthesis. In fed rats, incorporation of infused D-[1-_3Cjglucose occurred briskly; however, over 2 h there was no net glycogen accumulated. Degradation of labeled glycogen was greater in the fed versus the fasted rats (P < 0.001), and the lack of net glycogen synthesis in fed rats was due to degradation and synthesis occurring at similar rates throughout the infusion period. There was no indication that suppression of phosphorylase a or subsequent activation of glycogen synthase was involved in modulation of the flux of tracer into liver glycogen.We conclude that in both fed and fasted rats, glycogen synthase and phosphorylase are active simultaneously and the levels of liver glycogen reached during refeeding are determined by the balance between ongoing synthetic and degradative processes. (J. Clin. Invest. 1990. 86:612-617.) Key words: liver glycogen -in vivo NMR * phosphorylase * glycogen synthase Introduction After an overnight fast the rat liver is nearly depleted of glycogen stores. Repletion begins promptly upon feeding with both glucose and gluconeogenic substrates contributing to the formation of UDP-glucose and glycogen (1-6). The factors that control the transition of the liver from the glucose-producing to the glycogen-storing mode have been extensively studied, and include release of insulin into portal blood (7), suppression of glucagon secretion (8), and a rise in portal glucose concentration (9, 10). When isolated hepatocytes are incubated with high concentrations of glucose (1 1), and when mice are given large doses of glucose parenterally (12), near complete inactivation of phosphorylase a (GPa)' precedes the activation of glycogen synthase (GSi) and the onset of glycogen

Most of ADP·glucose linked to starch biosynthesis occurs outside the chloroplast in source leaves

“…This evidence is essentially in agreement with previous reports dealing with gluconeogenic processes in bacteria (31,32), animals (33,34), and heterotrophic plant cells (35,36). Accordingly, the newly proposed mechanism of starch biosynthesis, which is compatible with most, if not all, starchdeficient and excess mutant and transgenic plant described to date, assumes that gluconeogenic enzymes, such as plastid phosphoglucomutase and AGP, play a role in synthesizing ADPG from the glucose units that are derived from the starch breakdown (Fig.…”

Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo

“…USA 95 (1998) by mass isotopomer) appears to cycle through the glycogen pool prior to efflux from human liver (43). NMR data also corroborate that significant hepatic glucose-glycogen cycling occurs in vivo (44,45). These data support the conjecture that glycogenolysis inhibition could also reduce net gluconeogenic flux, and thereby contribute to the overall efficacy in reducing HGP in vivo.…”

Overexpression of Muscle Glycogen Phosphorylase in Cultured Human Muscle Fibers Causes Increased Glucose Consumption and Nonoxidative Disposal

“…It seems that a compensatory mechanism exists that tends to equilibrate the rates of glycogenolysis and glycogenesis to maintain glycogen turnover and net glycogen content. The simultaneous existence of both reactions or glycogen cycling has been clearly demonstrated in liver (37). Furthermore, in liver, glycogen turnover is greater in the fed state than in the fasted state (38), and thus it has been suggested that glycogen concentration may exert a regulatory effect on glycogen turnover.…”