Insulin, not glucose, controls hepatocellular glycogen deposition. A re-evaluation of the role of both agents in cultured liver cells.
The direct effects of insulin and glucose on glycogen accumulation were compared using monolayers of chicken embryo hepatocytes which, when cultured in chemically defined medium without hormones, retain viability for several days but become depleted of glycogen. The data strongly suggest that insulin is the major direct signal for hepatic glycogen synthesis, while glucose supports glycogen accumulation primarily in its role as a substrate. Insulin alone, when added to the cells in physiological concentrations, either shortly after isolation or throughout culture, restored glycogen to the maximal levels found in the liver of the fed chicken. Addition of increasing amounts of glucose in the absence of insulin, in contrast, yielded proportional but limited increases in glycogen deposition attaining not more than 30% of the maximal storage capacity of the cells. This hormone-independent glycogenesis was characterized by a 30-min burst of glycogen deposition immediately following a stepped increase of glucose, with no detectable change in glycogen synthase activity. Insulin-dependent glycogenesis evidenced a much slower rate of glycogen deposition and was accompanied by a near tripling of glycogen synthase activity. Insulin-induced glycogen stores were broken down following removal of the hormone, even when glucose was present in great excess, indicating that the cells require insulin to maintain as well as build up maximal levels of glycogen. In the presence of glucagon, insulin-induced glycogen stores were rapidly degraded, but glucose-induced glycogenesis was not inhibited. The actions of insulin and glucose in this system are both qualitatively and quantitatively similar to those that have been observed in the diabetic animal.
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D006006:Glycogen Synthase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000196:embryology; D008112:Liver Glycogen / Q000378:metabolism*; D008854:Microscopy, Electron; D013997:Time Factors
D007328:Insulin; D008112:Liver Glycogen; D005934:Glucagon; D006006:Glycogen Synthase; D005947:Glucose