Bariatric surgery in morbidly obese insulin resistant humans normalises insulin signalling but not insulin-stimulated glucose disposal.
dc.contributor.author | Chen, MZ | |
dc.contributor.author | Hudson, CA | |
dc.contributor.author | Vincent, EE | |
dc.contributor.author | de Berker, DAR | |
dc.contributor.author | May, MT | |
dc.contributor.author | Hers, I | |
dc.contributor.author | Dayan, CM | |
dc.contributor.author | Andrews, RC | |
dc.contributor.author | Tavaré, JM | |
dc.date.accessioned | 2019-01-30T12:47:08Z | |
dc.date.issued | 2015-04-13 | |
dc.description.abstract | AIMS: Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB), and compared this to lean volunteers. MATERIALS AND METHODS: The hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR) in eight morbidly obese (body mass index, BMI=47.3 ± 2.2 kg/m(2)) patients, before and after RYGB, and in eight lean volunteers (BMI=20.7 ± 0.7 kg/m2). Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50) and maximal (GDR100) GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity. RESULTS: Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001). Weight-loss of 29.9 ± 4 kg after surgery significantly improved GDR50 (P=0.004) but not GDR100 (P=0.3). These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001). Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA), and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA), and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively). CONCLUSIONS: Our data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss. | en_GB |
dc.description.sponsorship | Diabetes Research and Wellness Foundatio | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | Astra Zeneca | en_GB |
dc.identifier.citation | Vol. 10 (4), article e0120084 | en_GB |
dc.identifier.doi | 10.1371/journal.pone.0120084 | |
dc.identifier.uri | http://hdl.handle.net/10871/35646 | |
dc.language.iso | en | en_GB |
dc.publisher | Public Library of Science | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/25876175 | en_GB |
dc.rights | © 2015 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en_GB |
dc.subject | Adaptor Proteins, Signal Transducing | en_GB |
dc.subject | Adult | en_GB |
dc.subject | Bariatric Surgery | en_GB |
dc.subject | Female | en_GB |
dc.subject | Glucose | en_GB |
dc.subject | Humans | en_GB |
dc.subject | Insulin | en_GB |
dc.subject | Insulin Resistance | en_GB |
dc.subject | Male | en_GB |
dc.subject | Middle Aged | en_GB |
dc.subject | Obesity, Morbid | en_GB |
dc.subject | Phosphorylation | en_GB |
dc.subject | Proto-Oncogene Proteins c-akt | en_GB |
dc.subject | Signal Transduction | en_GB |
dc.subject | Young Adult | en_GB |
dc.title | Bariatric surgery in morbidly obese insulin resistant humans normalises insulin signalling but not insulin-stimulated glucose disposal. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-01-30T12:47:08Z | |
dc.identifier.issn | 1932-6203 | |
exeter.place-of-publication | United States | en_GB |
dc.description | This is the final published version. Available from PLoS via the DOI in this record. | en_GB |
dc.description | All relevant data are available from Figshare, under the DOI http://dx.doi. org/10.6084/m9.figshare.1292883. | en_GB |
dc.identifier.journal | PLoS ONE | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2015-01-19 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2015-01-19 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-01-30T12:43:31Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2019-01-30T12:47:11Z |
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