The Stimulation-Induced Increase in Skeletal Muscle Glycogen Synthase Content Is Impaired in Carriers of the Glycogen Synthase XbaI Gene Polymorphism
2001
Associations between glycogen synthase gene ( GYS1 ) polymorphism
and states of insulin resistance and type 2 diabetes have been reported. The
purpose of this study was to establish if the GYS1 genotype impacts
on the content of glycogen synthase (GS) protein in muscle measured under
basal and stimulated conditions. To examine this, GYS1 Xba I and
Met416Val polymorphisms and thigh muscle GYS1 protein content were determined
at rest, both before and after several weeks of neuromuscular electrical
stimulation in carriers and noncarriers of the mutations. The allelic
frequency was 0.086 for the Xba I mutation (A2) and 0.006 for the
Met416Val in our cohort of French-Canadian subjects. When measured at rest,
the GS protein content in muscle was similar among carriers and noncarriers of
the Xba I variant. However, the stimulation-induced increase (23%) in
the amount of GS muscle protein normally seen in wild-type individuals was
impaired in those carrying the Xba I mutation. These data demonstrate
that some individuals, because of their genetic background, are unable to
stimulate the process of GS protein accumulation in skeletal muscle. These
results could explain why some individuals appear to be genetically
predisposed to developing skeletal muscle insulin resistance when exposed to
unfavorable metabolic environments.
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