title: The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Modifies Exercise-Induced Muscle Metabolism.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Vaughan
authors.affiliation: Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester, United Kingdom.|Institute of Human Movement Sciences and Sport, ETH Zurich, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Brogioli
authors.affiliation: Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester, United Kingdom.|Institute of Human Movement Sciences and Sport, ETH Zurich, Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Maier
authors.affiliation: Chester Marathon, Chester, United Kingdom.
authors.forename: Andy
authors.initials: A
authors.lastname: White
authors.affiliation: Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Waldron
authors.affiliation: Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester, United Kingdom.
authors.forename: Jörn
authors.initials: J
authors.lastname: Rittweger
authors.affiliation: University Hospital Balgrist, University of Zurich, Zurich, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Toigo
authors.affiliation: University Hospital Balgrist, University of Zurich, Zurich, Switzerland.
authors.forename: Jessica
authors.initials: J
authors.lastname: Wettstein
authors.affiliation: Functional Genomics Center Zürich, UZH/ETHZ, Zurich, Switzerland.
authors.forename: Endre
authors.initials: E
authors.lastname: Laczko
authors.affiliation: Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester, United Kingdom.|University Hospital Balgrist, University of Zurich, Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Flück
mesh_terms: D015444:Exercise; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D005082:Physical Exertion; D011110:Polymorphism, Genetic
chemical_list: D007703:Peptidyl-Dipeptidase A