Salicylate potentiates the capacity of skeletal muscle cells to act as a glucose ‘sink’

Raid B. Nisr (Lead / Corresponding author), Emma Falconer, Alison D. McNeilly, Graham Rena

    Research output: Contribution to journalConference articlepeer-review


    Aims: The mechanisms of metabolic effects of salicylate (SA) in skeletal muscle are still unclear. Previous studies have shown that SA modulates glucose and fatty acids homeostasis. Here we have investigated the effects of SA on glucose uptake, insulin signalling, mitochondrial form and function, as well as key signalling pathways including AMPK, mTOR and NF-kB, in rat L6 skeletal muscle cells.

    Methods: 2DG uptake, Western Blotting, QPCR, confocal microscopy, Seahorse XF 24e

    Results: 1-5mM SA acutely increased basal oxygen consumption by 35-50% (p < 0.05-p < 0.001), and glucose uptake increased up to two-fold in L6 myotubes (p < 0.01-p < 0.001). SA (≥ 2mM) also activated AMPK, indicated by AMPK and ACC phosphorylation on T172 and Ser79 respectively, however minor or no effects seemed to be observed using other SA analogues. Palmitic acid (PA)-induced mitochondrial dysfunction and suppression of insulin-signalling were ablated by SA, possibly due to SA anti-inflammatory activity, as SA reduced IkBα loss and in addition, IL6 and COX-2 induction by nutrient overloading was suppressed by 80%. These effects of SA may be mediated at least in part by AMPK activity, as SA was less protective against PA induced effects on these readouts in stable α1-AMPK Knockdown L6 cells.

    Summary: In addition to its anti-inflammatory effects, SA is a mitochondrial membrane uncoupler which may directly reduce energy supply; however, effects on substrate oxidation (fatty acids and glucose), mediated at least in part by AMPK, are likely to potentiate the ability of muscle cells to act as a therapeutically important glucose ‘sink’.
    Original languageEnglish
    Article numberP31
    Pages (from-to)42
    Number of pages1
    JournalDiabetic Medicine
    Issue numberS1
    Publication statusPublished - Mar 2022


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