Author: Wright, David C.

Source: Applied Physiology, Nutrition, and Metabolism, Volume 32, Number 5, October 2007 , pp. 840-845(6)

Publisher: NRC Research Press

Abstract:

Regularly performed aerobic exercise leads to increases in skeletal muscle mitochondria and glucose transporter 4 (GLUT4) protein content, resulting in an enhanced capacity to oxidize substrates and improvements in insulin- and contraction-mediated glucose uptake. Although the specific mechanisms governing these adaptive responses have not been fully elucidated, accumulating evidence suggests that the increase in cytosolic Ca²⁺ that occurs with each wave of sacrolemmal depolarization is a key component of these processes. Treating L6 muscle cells with agents that increase Ca²⁺ without causing reductions in ~P or the activation of 5′-AMP-activated protein kinase leads to increases in GLUT4 and mitochondrial protein contents. This effect is likely controlled through calcium/calmodulin-dependent protein kinase (CaMK), since KN93, a specific CaMK inhibitor, blocks these adaptive responses. Recent findings provide evidence that the activation of p38 mitogen-activated protein kinase (MAPK) is involved in the pathway through which Ca²⁺/CaMK mediates mitochondrial and GLUT4 biogenesis. p38 MAPK initiates GLUT4 and mitochondrial biogenesis through the activation of transcription factors and transcriptional coactivators such as myocyte enhancer factor 2 (MEF2) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α). Subsequent increases in the content of these proteins further enhance Ca²⁺-induced GLUT4 and mitochondrial biogenesis. Since decreases in mitochondrial and GLUT4 contents are associated with skeletal muscle insulin resistance, an understanding of the mechanisms by which these processes can be normalized will aid in the prevention and treatment of type 2 diabetes.

La pratique régulière d'exercices aérobies augmente le contenu protéique du GLUT4 et des mitochondries dans le muscle squelettique produisant ainsi une meilleure capacité d'oxydation des substrats et une amélioration de la captation de glucose due à la contraction musculaire ou à l'action de l'insuline. Même si les mécanismes exacts à la base de ces adaptations ne sont pas encore totalement compris, de plus en plus d'observations scientifiques pointent vers l'augmentation du Ca²⁺ cytoplasmique se manifestant à chaque onde de dépolarisation du sarcolemme comme l'élément clé du processus. Le traitement des fibres musculaires L6 comportant des agents qui augmentent la concentration de Ca²⁺ sans réduire la concentration de ~P ni activer la 5′AMP protéine kinase cause l'augmentation du contenu protéique du GLUT4 et des mitochondries. Cet effet est probablement sous le contrôle de la protéine kinase calcium/calmoduline dépendante (CaMK), car KN93, un inhibiteur spécifique de la CaMK, empêche ces adaptations. Selon de récentes observations, l'activation par le mitogène de la p38 protéine kinase (MAPK), fait partie du processus par lequel Ca²⁺/CaMK intervient dans la biogenèse de la mitochondrie et du GLUT4. La p38 MAPK initie la biogenèse des mitochondries et du GLUT4 en activant les facteurs de transcription et les coactivateurs transcriptionnels tels MEF2 et PGC-1α. Une augmentation subséquente du contenu de ces protéines contribue à pousser plus loin la biogenèse des mitochondries et de GLUT4médiée par le calcium. Comme la diminution du contenu protéique des mitochondries et du GLUT4 est associée à l'insulinorésistance du muscle squelettique, la compréhension des mécanismes de normalisation de ces processus contribuera à la prévention et au traitement du diabète de type 2.

Document Type: Research article

Publication date: 2007-10-01

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• This bimonthly journal has a 30-year history of publishing, first as the Canadian Journal of Sport Sciences, and later as the Canadian Journal of Applied Physiology. It publishes original research articles, reviews, and commentaries, focussing on the application of physiology, nutrition, and metabolism to the study of human health, physical activity, and fitness. The published research, reviews, and symposia will be of interest to exercise physiologists, physical fitness and exercise rehabilitation specialists, public health and health care professionals, as well as basic and applied physiologists, nutritionists, and biochemists.
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