The many ways to regulate glucose transporter 4

Author: Klip, Amira

Source: Applied Physiology, Nutrition, and Metabolism, Volume 34, Number 3, June 2009 , pp. 481-487(7)

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Abstract:

Glucose uptake into skeletal muscle is primarily mediated by glucose transporter 4 (GLUT4). The number of GLUT4 polypeptides at the surface of muscle cells rises rapidly in response to insulin, contraction, depolarization, or energy deprivation. However, distinct mechanisms underlie the gain in surface GLUT4 in each case. Insulin promotes its exocytosis to the membrane, regulating vesicle movement, tethering, docking, and fusion. In contrast, muscle contraction, depolarization, and energy demand reduce GLUT4 endocytosis. The signals involved in each case also differ. Insulin utilizes Akt, Rabs, and selective actin remodelling, whereas depolarization and energy deprivation engage AMP-activated protein kinase and Ca²⁺-dependent signals. GLUT4 internalizes via 2 major routes that involve dynamin, but only one requires clathrin. The clathrin-independent route is slowed down by energy deprivation, and is regulated by AMP-activated protein kinase. In addition to regulation of the exocytic and endocytic movement of GLUT4, glucose uptake is also modulated through changes in the transporter's intrinsic activity. The glycolytic enzymes glyceraldehyde-3-dehydrogenase and hexokinase II contribute to such regulation, through differential binding to GLUT4.

La captation du glucose dans le muscle squelettique est principalement médiée par le transporteur du glucose 4 (GLUT4). Le nombre de polypeptides GLUT4 à la surface des cellules musculaires augmente rapidement en réponse à l'insuline, à la contraction musculaire, à la dépolarisation et à la privation d'énergie. Néanmoins, dans chaque condition, l'accumulation de GLUT4 à la surface des cellules est basée sur un mécanisme distinct. L'insuline déclenche son exocytose à la membrane, régularise le mouvement des vésicules, le câblage, l'ancrage et la fusion. Par contre, la contraction musculaire, la dépolarisation et la demande d'énergie diminuent l'endocytose du GLUT4. Les signaux diffèrent dans chaque condition. L'insuline utilise l'Akt, les Rabs et le remodelage spécifique de l'actine; la dépolarisation et la privation d'énergie utilisent l'AMP kinase (AMPK) et les signaux calciques dépendants. L'internalisation de GLUT4 se fait par deux routes principales qui intègrent la dynamine, mais seulement une route nécessite la clathrine. La route indépendante de la clathrine est ralentie par la privation d'énergie et est régulée par l'AMPK. Outre la régulation de l'exocytose et de l'endocytose du GLUT4, la captation du glucose est modulée par des modifications de l'activité intrinsèque du transporteur. La glycéraldéhyde-3 déshydrogénase et l'hexokinase II, des enzymes de la glycolyse, participent à cette régulation au moyen d'une liaison différente à GLUT4.

Document Type: Research article

Publication date: 2009-06-01

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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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The many ways to regulate glucose transporter 4

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