The impact of forearm immobilization and acipimox administration on muscle amino acid metabolism and insulin sensitivity in healthy, young volunteers
dc.contributor.author | Dirks, ML | |
dc.contributor.author | Jameson, TSO | |
dc.contributor.author | Andrews, RC | |
dc.contributor.author | Dunlop, MV | |
dc.contributor.author | Abdelrahman, DR | |
dc.contributor.author | Murton, AJ | |
dc.contributor.author | Wall, BT | |
dc.contributor.author | Stephens, FB | |
dc.date.accessioned | 2024-01-22T09:54:16Z | |
dc.date.issued | 2024-01-17 | |
dc.date.updated | 2024-01-21T08:59:33Z | |
dc.description.abstract | Although the mechanisms underpinning short-term muscle disuse atrophy and associated insulin resistance remain to be elucidated, perturbed lipid metabolism might be involved. Our aim was to determine the impact of acipimox administration (i.e. pharmacologically lowering circulating non-esterified fatty acid (NEFA) availability) on muscle amino acid metabolism and insulin sensitivity during short-term disuse. Eighteen healthy individuals (age 22±1 years, BMI 24.0±0.6 kg·m-2) underwent 2 days forearm immobilization with placebo (PLA; n=9) or acipimox (ACI; 250 mg Olbetam; n=9) ingestion four times daily. Before and after immobilization, whole-body glucose disposal rate (GDR), forearm glucose uptake (FGU, i.e. muscle insulin sensitivity), and amino acid kinetics were measured under fasting and hyperinsulinaemic-hyperaminoacidaemic-euglycaemic clamp conditions using forearm balance and L-[ring-2H5]-phenylalanine infusions. Immobilization did not affect GDR but decreased insulin-stimulated FGU in both groups; more so in ACI (from 53±8 to 12±5 µmol·min-1) than PLA (from 52±8 to 38±13 µmol·min-1; P<0.05). In ACI only, and in contrast to our hypothesis, fasting arterialised NEFA concentrations were elevated to 1.3±0.1 mmol·L-1 post-immobilization (P<0.05), and fasting forearm NEFA balance increased ~4-fold (P=0.10). Forearm phenylalanine net balance decreased following immobilization (P<0.10), driven by increased Ra (from 32±5 (fasting) and 21±4 (clamp) pre-immobilization to 53±8 and 31±4 post-immobilization; P<0.05) while Rd was unaffected by disuse or acipimox. Disuse-induced insulin resistance is accompanied by early signs of negative net muscle amino acid balance, which is driven by accelerated muscle amino acid efflux. Acutely elevated NEFA availability worsened muscle insulin resistance without affecting amino acid kinetics, suggesting increased muscle NEFA uptake may contribute to inactivity-induced insulin resistance but does not cause anabolic resistance. | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | National Institute of Aging | en_GB |
dc.format.medium | Print-Electronic | |
dc.identifier.citation | Published online 17 January 2024 | en_GB |
dc.identifier.doi | https://doi.org/10.1152/ajpendo.00345.2023 | |
dc.identifier.grantnumber | 209198/Z/17/Z | en_GB |
dc.identifier.grantnumber | P30-AG024832 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/135079 | |
dc.identifier | ORCID: 0000-0002-9189-1042 (Dirks, Marlou L) | |
dc.identifier | ResearcherID: G-5813-2011 (Dirks, Marlou L) | |
dc.language.iso | en | en_GB |
dc.publisher | American Physiological Society | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/38231001 | en_GB |
dc.rights | © 2024, American Journal of Physiology-Endocrinology and Metabolism. Open access under a Creative Commons Attribution 4.0 International licence | en_GB |
dc.subject | amino acid kinetics | en_GB |
dc.subject | disuse atrophy | en_GB |
dc.subject | insulin sensitivity | en_GB |
dc.subject | lipid | en_GB |
dc.subject | skeletal muscle | en_GB |
dc.title | The impact of forearm immobilization and acipimox administration on muscle amino acid metabolism and insulin sensitivity in healthy, young volunteers | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2024-01-22T09:54:16Z | |
dc.identifier.issn | 0193-1849 | |
exeter.place-of-publication | United States | |
dc.description | This is the author accepted manuscript. The final version is available on open access from the American Physiological Society via the DOI in this record | en_GB |
dc.identifier.eissn | 1522-1555 | |
dc.identifier.journal | American Journal of Physiology - Endocrinology and Metabolism | en_GB |
dc.relation.ispartof | Am J Physiol Endocrinol Metab | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2023-12-27 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2024-01-17 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2024-01-22T09:51:05Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2024-01-22T09:54:21Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2024-01-17 |
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