Endurance Training Alters Skeletal Muscle MCT Contents in T2DM Men

Abstract

Patients suffering from type 2 diabetes mellitus (T2DM) often exhibit chronic elevated lactate levels which can promote peripheral insulin resistance by disturbing skeletal muscle insulin-signaling. Monocarboxylate transporter (MCT) proteins transfer lactate molecules through cellular membranes. MCT-1 and MCT-4 are the main protein isoforms expressed in human skeletal muscle, with MCT-1 showing a higher affinity (lower Km) for lactate than MCT-4. T2DM patients have reduced membranous MCT-1 proteins. Consequently, the lactate transport between muscle cells and the circulation as well as within an intracellular lactate shuttle, involving mitochondria (where lactate can be further metabolized), can be negatively affected. This study investigates whether moderate cycling endurance training (3 times per week for 3 months) can change skele-tal muscle MCT contents in T2DM men (n=8, years=56±9, body mass index (BMI)=32±4 kg/m(2)). Protein content analyses (immuno-histochemical stainings) were performed in bio-psies taken from the vastus lateralis muscle. Intracellular MCT-1 proteins were up-regulated (relative increase+89%), while intracellular MCT-4 contents were down-regulated (relative decrease - 41%) following endurance training. Sarcolemmal MCT-1 and MCT-4 did not change. The question of whether the training-induced up-regulation of intracellular MCT-1 leads to an improved lactate transport (and clearance) in T2DM patients requires further research.

Changes in urine headspace composition as an effect of strenuous walking

“…Acetate and hexanoate are both transported through the cellular membrane by monocarboxylate transporter (MCT) proteins. These proteins have been shown to be altered by endurance training, and were studied with relation to possible up-regulation of the MCT-1 protein leading to improved clearance of lactate (Opitz et al 2014 ). An increase in clearance rates for hexanoate and acetate would make a plausible explanation for the increase in acetic and hexanoic acids seen in urine.…”

Hypoxia and Hyperoxia Affect Serum Angiogenic Regulators in T2DM Men during Cycling

“…They performed 40 min of submaximal cycle exercise on the upright bike "Ergometrics900" (Ergoline, Bitz, Germany) coupled to an ECG ("Ergoscript EK3012", Ergoline), with a constant absolute workload and at constant revolutions per minute [rpm = ~65] in all experimental runs. The individual workload [W] corresponded approxi-mately to the power that was determined at ≈ 2.5 mmol/l capillary blood lactate concentration during an endurance test that was performed prior to the experimental measurements (WHO step test: 25 W + 25 W every 2 min as described previously [26]). The average workload that was used in the experimental runs was 82 ± 27 W.…”

The Proposal of Molecular Mechanisms of Weak Organic Acids Intake-Induced Improvement of Insulin Resistance in Diabetes Mellitus via Elevation of Interstitial Fluid pH

“…In most mammalian cells, MCTs play an important role in extrusion of lactic acid and other monocarboxylic acids such pyruvic acid, beta-hydroxybutyric acid and acetoacetic acid from the cytosolic space to the extracellular space across the cellular membrane ( Figure 3 B) [ 144 , 145 , 146 ]. Expression of MCTs is altered in diabetes mellitus [ 147 , 148 ]. Since MCTs transport monocarboxylic acid coupled with H + , MCTs function in the process of H + extrusion coupled with extrusion of monocarboxylic acid (MC) ( Figure 3 B).…”