TY - JOUR

T1 - Exercise-stimulated glucose uptake - regulation and implications for glycaemic control

AU - Sylow, Lykke

AU - Kleinert, Maximilian

AU - Richter, Erik A.

AU - Jensen, Thomas Elbenhardt

N1 - CURIS 2017 NEXS 054

PY - 2017

Y1 - 2017

N2 - Skeletal muscle extracts glucose from the blood to maintain demand for carbohydrates as an energy source during exercise. Such uptake involves complex molecular signalling processes that are distinct from those activated by insulin. Exercise-stimulated glucose uptake is preserved in insulin-resistant muscle, emphasizing exercise as a therapeutic cornerstone among patients with metabolic diseases such as diabetes mellitus. Exercise increases uptake of glucose by up to 50-fold through the simultaneous stimulation of three key steps: delivery, transport across the muscle membrane and intracellular flux through metabolic processes (glycolysis and glucose oxidation). The available data suggest that no single signal transduction pathway can fully account for the regulation of any of these key steps, owing to redundancy in the signalling pathways that mediate glucose uptake to ensure maintenance of muscle energy supply during physical activity. Here, we review the molecular mechanisms that regulate the movement of glucose from the capillary bed into the muscle cell and discuss what is known about their integrated regulation during exercise. Novel developments within the field of mass spectrometry-based proteomics indicate that the known regulators of glucose uptake are only the tip of the iceberg. Consequently, many exciting discoveries clearly lie ahead.

AB - Skeletal muscle extracts glucose from the blood to maintain demand for carbohydrates as an energy source during exercise. Such uptake involves complex molecular signalling processes that are distinct from those activated by insulin. Exercise-stimulated glucose uptake is preserved in insulin-resistant muscle, emphasizing exercise as a therapeutic cornerstone among patients with metabolic diseases such as diabetes mellitus. Exercise increases uptake of glucose by up to 50-fold through the simultaneous stimulation of three key steps: delivery, transport across the muscle membrane and intracellular flux through metabolic processes (glycolysis and glucose oxidation). The available data suggest that no single signal transduction pathway can fully account for the regulation of any of these key steps, owing to redundancy in the signalling pathways that mediate glucose uptake to ensure maintenance of muscle energy supply during physical activity. Here, we review the molecular mechanisms that regulate the movement of glucose from the capillary bed into the muscle cell and discuss what is known about their integrated regulation during exercise. Novel developments within the field of mass spectrometry-based proteomics indicate that the known regulators of glucose uptake are only the tip of the iceberg. Consequently, many exciting discoveries clearly lie ahead.

KW - Faculty of Science

KW - Energy metabolism

KW - Insulin signalling

KW - Metabolism

KW - Skeletal muscle

KW - Type 2 diabetes

U2 - 10.1038/nrendo.2016.162

DO - 10.1038/nrendo.2016.162

M3 - Review

C2 - 27739515

VL - 13

SP - 133

EP - 148

JO - Nature Reviews Endocrinology

JF - Nature Reviews Endocrinology

SN - 1759-5029

IS - 3

ER -