CELL SWELLING AND GLYCOGEN-METABOLISM IN HEPATOCYTES FROM FASTED RATS

Cell swelling is known to increase net glycogen production from glucos e in hepatocytes from fasted rats by activating glycogen synthase. Sin ce both active glycogen synthase and phosphorylase are present in hepa tocytes, suppression of flux through phosphorylase may also contribute to the net increase in glycogen synthesis by cell swelling. We have d eveloped an isotopic procedure to estimate the fluxes through glycogen synthase and phosphorylase in intact hepatocytes and we have examined the effect of cell swelling on both enzyme fluxes. The following obse rvations were made. (1) Hypotonic or glutamine-induced cell swelling i ncreased net glycogen production by activating flux through glycogen s ynthase with little effect on phosphorylaseflux. Proline, previously s hown to increase glycogen synthesis more than could be accounted for b y its ability to cause cell swelling, increased flux through glycogen synthase and inhibited phosphorylase flux. (2) Incorporation of [C-14] glucose into glycogen preceded complete mixing of [C-14]glucose with t he intracellular pool of UDPglucose. It is concluded that cell swellin g affects glycogen synthase only and that UDPglucose is compartmentali zed.