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Insulin action in denervated skeletal muscle

Thesis/Dissertation ·
OSTI ID:7164340
The goal of this study was to determine the mechanisms responsible for reduced insulin response in denervated muscle. Denervation for 3 days of rat muscles consisting of very different compositions of fiber types decreased insulin stimulated (U-/sup 14/C)glucose incorporation into glycogen by 80%. Associated with the reduction in glycogen synthesis was a decreased activation of glycogen synthase. Denervation of hemidiaphragms for 1 day decreased both the basal and insulin stimulated activity ratios of glycogen synthase and the rate of insulin stimulated (U-/sup 14/C(glucose incorporation into glycogen by 50%. Insulin stimulation of 2-deoxy(/sup 3/H)glucose uptake was not decreased until 3 days after denervation. Consistent with the effects on glucose transport,insulin did not increase the intracellular concentration of glucose-6-P in muscles 3 days after denervation. Furthermore, since the Ka for glucose-6-P activation of glycogen synthase was not decreased by insulin in denervated hemidiaphragms, the effects of denervation on glycogen synthase and glucose transport were synergistic resulting in the 80% decrease in glycogen synthesis rates.
Research Organization:
Washington Univ., St. Louis, MO (USA)
OSTI ID:
7164340
Country of Publication:
United States
Language:
English