Title:A Primary Reduced TCA Flux Governs Substrate Oxidation in T2D Skeletal Muscle
VOLUME: 8 ISSUE: 6
Author(s):Michael Gaster
Affiliation:Department Laboratory of molecular physiology Dept. of Pathology Odense University Hospital DK- 5000 Odense Denmark.
Keywords:Glucose oxidation, Human, Insulin resistance, Lipid oxidation, Metabolic inflexibility, Mitochondria, Myotubes,
oxidative phosphorylation, Skeletal muscle, Tricarboxylic acid cycle, Type 2 diabetes.
Abstract:Our current knowledge on substrate oxidation in skeletal muscle in relation to insulin resistance and type 2 diabetes
(T2D) originate mainly from in vivo studies. The oxidative capacity of skeletal muscle is highly influenced by
physical activity, ageing, hormonal status, and fiber type composition, rendering it difficult to determine the contribution
of heritable factors to the alteration in oxidative metabolism. Cultured human myotubes offer a unique model to distinguish
between primary and environmental factors in the etiology of insulin resistance. The objective of this review is to
summarise our studies on substrate oxidation in human myotubes established from lean, obese and T2D subjects, especially
focusing on whether the increased respiratory quotient seen in T2D subjects is based on primary traits and whether
changes in substrate oxidation may have a common explanation. Obtained results add further regulatory mechanism to our
understanding of substrate oxidation in human skeletal muscle during normo- an pathophysiological conditions, focusing
especially on the governing influence of a primary reduced TCA flux for the diabetic phenotype in skeletal muscle.
