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Post-translational dysregulation of glucose uptake during exhaustive cycling exercise in vastus laterals muscle of healthy homozygous carriers of the ACE deletion allele

Flück, Martin and Vaughan, David and Rittweger, Jörn and Giraud, Marie-Noelle (2022) Post-translational dysregulation of glucose uptake during exhaustive cycling exercise in vastus laterals muscle of healthy homozygous carriers of the ACE deletion allele. Frontiers in Physiology, 13, p. 933792. Frontiers Media S.A. doi: 10.3389/fphys.2022.933792. ISSN 1664-042X.

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Official URL: https://doi.org/10.3389/fphys.2022.933792


Homozygous carriers of the deletion allele in the gene for angiotensin-converting enzyme (ACE-DD) demonstrate an elevated risk to develop inactivity-related type II diabetes and show an overshoot of blood glucose concentration with enduring exercise compared to insertion allele carriers. We hypothesized that ACE-DD genotypes exhibit a perturbed activity of signaling processes governing capillary-dependent glucose uptake in vastus lateralis muscle during exhaustive cycling exercise, which is associated with the aerobic fitness state. 27 healthy, male white Caucasian subjects (26.8 ± 1.1 years; BMI 23.6 +/- 0.6 kg m-2) were characterized for their aerobic fitness based on a threshold of 50 ml O2 min-1 kg-1 and the ACE-I/D genotype. Subjects completed a session of exhaustive one-legged exercise in the fasted state under concomitant measurement of cardiorespiratory function. Capillary blood and biopsies were collected before, and ½ and 8 h after exercise to quantify glucose and lipid metabolism-related compounds (lipoproteins, total cholesterol, ketones) in blood, the phosphorylation of 45 signaling proteins, muscle glycogen and capillaries. Effects of aerobic fitness, ACE-I/D genotype, and exercise were assessed with analysis of variance (ANOVA) under the hypothesis of a dominant effect of the insertion allele. Exertion with one-legged exercise manifested in a reduction of glycogen concentration ½ h after exercise (-0.046 mg glycogen mg-1 protein). Blood glucose concentration rose immediately after exercise in association with the ACE-I/D genotype (ACE-DD: +26%, ACE-ID/II: +6%) and independent of the fitness state (p = 0.452). Variability in total cholesterol was associated with exercise and fitness. In fit subjects, the phosphorylation levels of glucose uptake-regulating kinases [AKT-pT308 (+156%), SRC-pY419, p38α-pT180/T182, HCK-pY411], as well as cytokine/angiotensin 1-7 signaling factors [(STAT5A-pY694, STAT5B-pY699, FYN-pY420, EGFR-pY1086] were higher in angiotensin converting enzyme I-allele carriers than ACE-DD genotypes after exercise. Conversely, the AKT-S473 phosphorylation level (+117%) and angiotensin 2's blood concentration (+191%) were higher in ACE-DD genotypes. AKT-S473 phosphorylation levels post-exercise correlated to anatomical parameters of muscle performance and metabolic parameters (p < 0.05 and │r│>0.70). The observations identify reciprocal alterations of S473 and T308 phosphorylation of AKT as gatekeeper of a post-translational dysregulation of transcapillary glucose uptake in ACE-DD genotypes which may be targeted in personalized approaches to mitigate type II diabetes

Item URL in elib:https://elib.dlr.de/190594/
Document Type:Article
Title:Post-translational dysregulation of glucose uptake during exhaustive cycling exercise in vastus laterals muscle of healthy homozygous carriers of the ACE deletion allele
AuthorsInstitution or Email of AuthorsAuthor's ORCID iD
Flück, Martinmartin.flueck (at) unifr.chUNSPECIFIED
Vaughan, DavidManchester Metropolitan University, United KingdomUNSPECIFIED
Rittweger, JörnJoern.Rittweger (at) dlr.dehttps://orcid.org/0000-0002-2223-8963
Giraud, Marie-Noellemarie-noelle.giraud (at) unifr.chUNSPECIFIED
Date:6 September 2022
Journal or Publication Title:Frontiers in Physiology
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In ISI Web of Science:Yes
Page Range:p. 933792
Publisher:Frontiers Media S.A
Keywords:angiotensin; diabetes; exercise; genotype; signalling
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Research under Space Conditions
DLR - Research theme (Project):R - Muscle Mechanics and Metabolism
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Muscle and Bone Metabolism
Deposited By: Kaiser-Stolz, Claudia
Deposited On:23 Nov 2022 09:48
Last Modified:02 Dec 2022 09:15

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