Inhibition of glycogen synthesis in rat hepatocytes by medium Zn2+.
In hepatocytes from fasted rats, Zn2+ in the range from 0 to 500 microM has relatively minor effects on gluconeogenesis from most substrates, or on ureagenesis from NH3. In hepatocytes from fed rats, Zn2+ does not affect glycogenolysis. In hepatocytes from fasted rats, in which glycogen is being actively synthesized using the substrate combination (Katz et al. (1976) Proc. Natl.Acad.Sci.USA 73,3433-3437) of glucose, lactate and glutamine (all 10mM), Zn2+ markedly inhibits glycogen synthesis, with total inhibition at 500 microM, and a half maximal effect in the range from 50 to 100 microM. Dipicolinate (pyridine 2,6-dicarboxylate), a zinc chelator, is about as effective as L-glutamine in activating glycogen synthesis with the substrate combination of dihydroxyacetone, lactate and glucose (all 10mM). This suggests the possible hypothesis that endogenous Zn2+ might control the rate of glycogen synthesis in vivo. However, alternate explanations such as metabolite accumulation are also possible, since dipicolinate causes inhibition of gluconeogenesis from L-lactate.
D000818:Animals; D002250:Carbon Radioisotopes; D002712:Chlorides; D005943:Gluconeogenesis / Q000187:drug effects; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008112:Liver Glycogen / Q000096:biosynthesis*; D051381:Rats; D015032:Zinc / Q000494:pharmacology*; D017967:Zinc Compounds
D002250:Carbon Radioisotopes; D002712:Chlorides; D008112:Liver Glycogen; D017967:Zinc Compounds; C016837:zinc chloride; D015032:Zinc