Skeletal muscle insulin resistance is a key feature of Type 2 diabetes and is closely related to impaired glucose uptake. Inulin‐type fructans are commonly used as dietary fibers, but their direct effects on insulin‐responsive cells are not well defined. In the present study, the effect of chicory inulin on palmitate‐induced insulin resistance was examined in C2C12 myotubes. Chicory inulin was characterized before use. Palmitate treatment reduced glucose uptake and disrupted insulin signaling in C2C12 myotubes. Treatment with chicory inulin increased glucose uptake and promoted GLUT4 translocation. Inhibitory phosphorylation of IRS‐1 was also reduced. In addition, mitochondrial membrane potential and ATP levels were improved, while the production of inflammatory cytokines was decreased. The expression of SNX27 was increased in cells treated with chicory inulin. Overexpression of SNX27 showed similar effects on glucose uptake and insulin signaling. Silencing of SNX27 weakened these effects. Changes in PI3K/AKT and NF‐κB signaling were observed under the same conditions. Taken together, CI exposure was associated with improved insulin‐resistance‐related cellular responses in PA‐treated C2C12 myotubes. These effects may involve SNX27‐associated processes. These findings should be interpreted as exploratory cellular‐level evidence obtained under controlled in vitro conditions, rather than as direct evidence that intact dietary inulin reaches skeletal muscle or produces the same effects in vivo.
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