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dc.contributor.author
Vaughan, David
dc.contributor.author
Brogioli, Michael
dc.contributor.author
Maier, Thomas
dc.contributor.author
White, Andy
dc.contributor.author
Waldron, Sarah
dc.contributor.author
Rittweger, Jörn
dc.contributor.author
Toigo, Marco
dc.contributor.author
Wettstein, Jessica
dc.contributor.author
Laczko, Endre
dc.contributor.author
Flück, Martin
dc.date.accessioned
2018-08-23T08:48:15Z
dc.date.available
2017-06-12T03:36:05Z
dc.date.available
2018-08-23T08:48:15Z
dc.date.issued
2016-03-16
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0149046
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/114786
dc.identifier.doi
10.3929/ethz-b-000114786
dc.description.abstract
Objective A silencer region (I-allele) within intron 16 of the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is implicated in phenotypic variation of aerobic fitness and the development of type II diabetes. We hypothesised that the reportedly lower aerobic performance in non-carriers compared to carriers of the ACE I-allele, i.e. ACE-DD vs. ACE-ID/ACE-II genotype, is associated with alterations in activity-induced glucose metabolism and capillarisation in exercise muscle. Methods Fifty-three, not-specifically trained Caucasian men carried out a one-legged bout of cycling exercise to exhaustion and/or participated in a marathon, the aim being to identify and validate genotype effects on exercise metabolism. Respiratory exchange ratio (RER), serum glucose and lipid concentration, glycogen, and metabolite content in vastus lateralis muscle based on ultra-performance lipid chromatography-mass spectrometry (UPLC-MS), were assessed before and after the cycling exercise in thirty-three participants. Serum metabolites were measured in forty subjects that completed the marathon. Genotype effects were assessed post-hoc. Results Cycling exercise reduced muscle glycogen concentration and this tended to be affected by the ACE I-allele (p = 0.09). The ACE-DD genotype showed a lower maximal RER and a selective increase in serum glucose concentration after exercise compared to ACE-ID and ACE-II genotypes (+24% vs. +2% and –3%, respectively). Major metabolites of mitochondrial metabolism (i.e. phosphoenol pyruvate, nicotinamide adenine dinucleotide phosphate, L-Aspartic acid, glutathione) were selectively affected in vastus lateralis muscle by exercise in the ACE-DD genotype. Capillary-to-fibre ratio was 24%-lower in the ACE-DD genotype. Individuals with the ACE-DD genotype demonstrated an abnormal increase in serum glucose to 7.7 mM after the marathon. Conclusion The observations imply a genetically modulated role for ACE in control of glucose import and oxidation in working skeletal muscle. ACE-DD genotypes thereby transit into a pre-diabetic state with exhaustive exercise, which relates to a lowered muscle capillarisation, and deregulation of mitochondria-associated metabolism.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Modifies Exercise-Induced Muscle Metabolism
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
PLoS ONE
ethz.journal.volume
11
en_US
ethz.journal.issue
3
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e0149046
en_US
ethz.size
20 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
006206116
ethz.publication.place
San Francisco, CA, USA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung & Wirtschaftsbez. / Domain VP Research & Corporate Relations::02207 - Functional Genomics Center Zürich / Functional Genomics Center Zürich
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung & Wirtschaftsbez. / Domain VP Research & Corporate Relations::02207 - Functional Genomics Center Zürich / Functional Genomics Center Zürich
ethz.date.deposited
2017-06-12T03:39:15Z
ethz.source
ECIT
ethz.identifier.importid
imp593654460058661405
ethz.ecitpid
pub:176590
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-31T16:11:46Z
ethz.rosetta.lastUpdated
2018-11-07T23:39:28Z
ethz.rosetta.versionExported
true
ethz.COinS
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