Exercise-induced muscle metabolism exposes genetic risk to develop diabetes

International Conference and Exhibition on Molecular Medicine and Diagnostics

August 24-26, 2015 London, UK

Martin Fluck

Scientific Tracks Abstracts: J Mol Genet Med

Abstract :

Hypoperfusion of skeletal muscle due to resistance to insulin-mediated vasodilation is an early hallmark of a cluster of metabolic
diseases that represent a major economic substrate for the medical industry. Absence of an insertion sequence (the I-allele) in
the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is associated with reduced aerobic fitness
and the development of type 2 diabetes. Our investigations identify out of norm elevations in serum glucose concentration after the
metabolic challenge of exhaustive endurance exercise in ACE-DD genotypes that do not carry the ACE I-allele. Explorative assessment
of the muscle metabolome and transcriptome exposed that the defect involves a reduced oxidation of glucose and compensatory
adjustments in mitochondria-associated pyruvate and amino acid metabolism; all of which corresponded to a reduced muscle
capillarisation and elevated serum levels of the ACE product, angiotensin 2. Compared to ACE-II genotypes, ACE-DD genotypes
had a lower capacity for oxygen extraction during exhaustive exercise and the subsequent response in mitochondrial biogenesis was
blunted. Anti-hypertensive treatment with ACE inhibitor pronouncedly modulated mitochondrial and angiogenic gene expression
in exercised muscle. Our observations imply that the monitoring of glucose import and combustion in working muscle exposes the
genetic risk of developing metabolic disease.

Biography :

Martin Fluck is the Professor for Muscle Plasticity located at the Balgrist Hospital of the University of Zurich. His research centers on the adaptive pathways governing
skeletal muscle function with specific focus on an integrative omics approach. He has published over 70 articles in peer reviews journal (H-index>24) and has served as
an Editorial Board Member of repute.