Reduced glycogen phosphorylase activity in denervated hindlimb muscles of rat is related to muscle atrophy and fibre type

Changes in the activity of muscle glycogen synthase or phosphorylase (GP) m ay be responsible for the deregulation of glycogen synthesis and storage wh ich occurs in diabetes mellitus. To clarify the relationship between muscle atrophy, fibre type, insulin-stimulated glucose uptake and GP activity dur ing insulin resistance, we used sciatic nerve severance to induce insulin r esistance in rat hindlimb muscles and compared the above parameters in musc les with a range of fibre types. Changes were analysed by comparison with t he contralateral hindlimb, which bears more weight due to denervation of th e opposing limb, as well as the sham-operated and contralateral, limb of a separate rat. Denervation caused a decrease in insulin-stimulated glucose u ptake by 1 day after denervation and a decline of GP activity after 7 days in all muscles investigated. GP activity decreased by 73% in soleus, 36% in red gastrocnemius, 35% in tibialis and 13% in white gastrocnemius, which w as related to the degree of muscle atrophy and inversely related to the ove rall GP activity in non-denervated muscles. GP activity in muscles of the c ontralateral limb from the denervated rat did not differ from either hindli mb of the sham-operated rat. We conclude that the fibre-type related reduct ion in insulin-stimulated glucose uptake of denervated muscle determines th e change in its metabolism and it is this metabolic change which determines the mechanism, rate and degree of muscle atrophy, which is directly relate d to the decline in GP activity.