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J. Biol. Chem., Vol. 259, Issue 4, 2201-2207, 02, 1984
RL Smith and JC Lawrence Jr
Rat hemidiaphragms were denervated in vivo and then incubated in vitro to
assess the ability of insulin to stimulate glycogen synthesis. Denervation
for 1 day resulted in 50% decreases in the stimulation by insulin of
[U-14C]glucose incorporation into glycogen, and in both the basal and the
insulin-stimulated activity ratios (activity minus glucose-6-P/activity
plus glucose-6-P) of glycogen synthase; however, the stimulation of
2-deoxyglucose uptake by insulin was not affected by 1 day of denervation.
The hormonal stimulation of [U-14C]glucose into glycogen was decreased by
90% after 3 days of denervation. At this time, the stimulation of
2-deoxyglucose uptake by insulin was also reduced and the synthase activity
ratios remained depressed. Consistent with its reduced effect on glucose
transport, the hormone did not increase glucose-6-P in the 3-day denervated
muscles. Furthermore, the Ka for activation of glycogen synthase by
glucose-6-P was higher in denervated muscles, and denervation abolished the
effect of insulin on decreasing the Ka. The results presented demonstrate
that denervation rapidly reduces the extent to which glycogen synthase can
be activated by insulin, and has a later effect on decreasing the
stimulation of glucose transport. These two effects act synergistically to
markedly decrease the hormonal stimulation of glycogen synthesis.
Insulin action in denervated rat hemidiaphragms. Decreased hormonal stimulation of glycogen synthesis involves both glycogen synthase and glucose transport
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