Mechanisms limiting glycogen storage in muscle during prolonged insulin stimulation
Richter, E.A.; Hansen, S.A.; Hansen, B.F.
American Journal of Physiology 255(5 Pt 1): E621-E628
1988
ISSN/ISBN: 0002-9513 PMID: 3142271 Document Number: 324242
The extent to which muscle glycogen concentration can be increased during exposure to maximal insulin concentrations and abundant glucose was investigated in the isolated perfused rat hindquarter preparation. Perfusion for 7 h in the presence of 20,000 .mu.U/ml insulin and 11-13 mM glucose increased muscle glycogen concentrations to maximal values 2, 3, and 3.5 times above normal fed levels in fast-twitch white, slow-twitch red, and fast-twitch red fibers, respectively. Glucose uptake decreased (mean .+-. SE) from 34.9 .+-. 1.2 .mu.mol .cntdot. g-1 .cntdot. h-1 at O h to 7.5 .+-. 0.7 after 7 h of perfusion. During the perfusion muscle glycogen synthase activity decreased and free intracellular glucose and glucose 6-phosphate increased indicating that glucose disposal was impaired. However, glucose transport as measured by the uptake of 3-O-[14C]methyl-D-glucose was also markedly decreased after 5 and 7 h of perfusion compared with initial values. Total muscle water concentration decreased during glycogen loading of the muscles. Mechanisms limiting glycogen storage under maximal insulin stimulation include impaired insulin-stimulated membrane transport of glucose as well as impaired intracellular glucose disposal.