Constitutive mTORC1 Activation in Skeletal Muscle Increases Inflammation but is not Sufficient to Impair Glucose Tolerance.

Marchant ED; Kalenta H; Kilroe SP; May J; Martini WZ; Weldon KS et al. · 2026 · Function (Oxford, England) · Atlas ID MARCHANT2026

Constitutive mTORC1 activation in mouse skeletal muscle (via GATOR1 complex KO) increases inflammatory markers but is not sufficient to impair glucose tolerance, indicating that additional metabolic inputs beyond muscle mTORC1 hyperactivation are required to drive insulin resistance.

At a glance

Evidence tierC Animal in vivo
Study type4 - Animal Study
Model systemMouse
JournalFunction (Oxford, England)
Year2026
Peer reviewedYes
SourceDOI 10.1152/function.039.2026

Abstract

Aberrant mTORC1 signaling in skeletal muscle has been implicated in aging and insulin resistance, however, it is not known whether chronic mTORC1 activation directly causes glucose intolerance. We tested the hypothesis that constitutive mTORC1 activation in mouse skeletal muscle impairs glucose homeostasis using tamoxifen-inducible, muscle-specific GATOR1 complex knockout.

Extracted findings

InterventionConstitutive mTORC1 activation (GATOR1 muscle-specific KO)
TargetmTORC1 / GATOR1 complex
ModelMouse
EffectIncreased skeletal muscle inflammation without impairment of glucose tolerance

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