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Publication
Key glycolytic enzyme activities of skeletal muscle are decreased under fed and
fasted states in mice with knocked down levels of Shc proteins.
Authors Hagopian K, Tomilov AA, Kim K, Cortopassi GA, Ramsey JJ
Submitted By Jon Ramsey on 7/24/2015
Status Published
Journal PLoS ONE
Year 2015
Date Published
Volume : Pages 10 : e0124204
PubMed Reference 25880638
Abstract Shc proteins interact with the insulin receptor, indicating a role in regulating
glycolysis. To investigate this idea, the activities of key glycolytic
regulatory enzymes and metabolites levels were measured in skeletal muscle from
mice with low levels of Shc proteins (ShcKO) and wild-type (WT) controls. The
activities of hexokinase, phosphofructokinase-1 and pyruvate kinase were
decreased in ShcKO versus WT mice under both fed and fasted conditions.
Increased alanine transaminase and branched-chain amino acid transaminase
activities were also observed in ShcKO mice under both fed and fasting
conditions. Protein expression of glycolytic enzymes was unchanged in the ShcKO
and WT mice, indicating that decreased activities were not due to changes in
their transcription. Changes in metabolite levels were consistent with the
observed changes in enzyme activities. In particular, the levels of
fructose-2,6-bisphosphate, a potent activator of phosphofructokinase-1, were
consistently decreased in the ShcKO mice. Furthermore, the levels of lactate
(inhibitor of hexokinase and phosphofructokinase-1) and citrate (inhibitor of
phosphofructokinase-1 and pyruvate kinase) were increased in fed and fasted
ShcKO versus WT mice. Pyruvate dehydrogenase activity was lower in ShcKO versus
WT mice under fed conditions, and showed inhibition under fasting conditions in
both ShcKO and WT mice, with ShcKO mice showing less inhibition than the WT
mice. Pyruvate dehydrogenase kinase 4 levels were unchanged under fed conditions
but were lower in the ShcKO mice under fasting conditions. These studies
indicate that decreased levels of Shc proteins in skeletal muscle lead to a
decreased glycolytic capacity in both fed and fasted states.




Strains
StrainDevelopment StatusCreation MethodOptions
B6.Cg-Shc1tm1PgpPhenotyping ongoingknockout
View




Genes
SymbolDescription
Shc1src homology 2 domain-containing transforming protein C1

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