Immobilisation induces sizeable and sustained reductions in forearm glucose uptake in just 24 h but does not change lipid uptake in healthy men

© 2021 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society Key points: The trajectory, magnitude and localisation of metabolic perturbations caused by immobilisation (IMM) are unresolved. Forearm glucose uptake (FGU) in response to glucose feeding was determined in healthy men before and during 72h of forearm IMM, and the same measurements were made in the non-IMM contralateral limb at baseline and 72h. In a similar study design, FGU and forearm lipid uptake were determined after a high fat mixed-meal (HFMM) in IMM and non-IMM limbs. FGU was reduced by 38%, 57% and 46% following 24, 48 and 72h IMM, respectively, but was unchanged in the non-IMM limb. A similar FGU response to IMM was observed after a HFMM, and forearm lipid uptake was unchanged. A sizeable reduction in FGU occurs in just 24h of IMM, which is sustained thereafter and specific to the IMM limb, making unloading per se the likely rapid driver of dysregulation. Abstract: The trajectory and magnitude of metabolic perturbations caused by muscle disuse are unknown yet central to understanding the mechanistic basis of immobilisation-associated metabolic dysregulation. To address this gap, forearm glucose uptake (FGU) was determined in 10healthy men (age 24.9±0.6years, weight 71.9±2.6 kg, BMI 22.6±0.6kg/m2) during a 180min oral glucose challenge before (0) and after 24, 48 and 72h of arm immobilisation, and before and after 72h in the contralateral non-immobilised arm (Study A). FGU was decreased from baseline at 24h (38%, P=0.04), 48h (57%, P=0.01) and 72h (46%, P=0.06) of immobilisation, and was also 63% less than the non-immobilised limb at 72h (P=0.002). In a second study, FGU and forearm lipid uptake were determined in ninehealthy men (age 22.4±1.3years, weight 71.4±2.8kg, BMI 22.6±0.8kg/m2) during a 420min mixed-meal challenge before (0) and after 24 and 48h of arm immobilisation and before and after 72h in the contralateral non-immobilised arm (Study B). FGU responses were similar to Study A, and forearm lipid uptake was unchanged from pre-immobilisation in both arms over the study. A sizeable decrement in FGU in response to glucose feeding occurred within 24h of immobilisation that was sustained and specific to the immobilised limb. Increasing lipid availability had no additional impact on the rate or magnitude of these responses or on lipid uptake. These findings highlight a lack of muscle contraction per se as a fast-acting physiological insult to FGU.