Résumés
Résumé
La régulation et le maintien d’un état métabolique normal dépend d’un système d’homéostasie complexe incluant de nombreux organes et tissus. Des défauts acquis dans ce système associés à des facteurs environnementaux mènent au développement d’anomalies métaboliques comme le syndrome X, qui est devenu un syndrome fréquent dans les pays industrialisés. Ce syndrome se caractérise par l’association d’anomalies incluant une résistance à l’insuline, un hyper-insulinisme, une intolérance au glucose ou un diabète de type 2, une hypertension artérielle et des troubles du métabolisme lipidique et de la coagulation. Sa gravité résulte de la fréquence des complications cardiovasculaires associées à ces altérations. La résistance à l’insuline du tissu adipeux (en particulier viscéral) et du muscle, qui se répercute sur le métabolisme hépatique, et les altérations des flux de substrats métaboliques entre ces tissus jouent un rôle majeur dans sa physiopathologie. De nouvelles classes pharmacologiques viennent enrichir l’arsenal thérapeutique et semblent prometteuses pour traiter l’insulinorésistance. À cet égard, le tissu adipeux n’est plus simplement considéré comme un simple tissu de stockage des réserves graisseuses, mais comme un organe jouant un rôle actif dans la régulation métabolique. Le tissu adipeux sécrète, en effet, une grande variété de molécules biologiquement actives agissant pour prévenir l’accumulation délétère de lipides et la modulation de l’insulinorésistance. Cet article a pour objectif de mieux comprendre les mécanismes menant à l’insulinorésistance et au diabète de type 2, selon les plus récentes avancées dans la connaissance du rôle et des interactions d’hormones spécifiquement issues de l’adipocyte, récemment identifiées, et appelées adipocytokines ou adipokines.
Summary
Normal metabolic balance is maintained by a complex homeostatic system involving multiple tissues and organs. Acquired or inherited defects associated to environmental factors in any part of this system can lead to metabolic disorders such as the syndrome X which is presently a frequent syndrome in industrialized countries. It is characterized by a cluster of risk factors of atherosclerosis including insulin resistance, hyperinsulinemia, impaired glucose tolerance or type 2 diabetes, hypertension, dyslipidemia, and coagulation abnormalities. Its pathophysiology is likely to involve insulin resistance at the level of both skeletal muscle and visceral adipose tissue and altered fluxes of metabolic substrates between these tissues that in turn impair liver metabolism. Therapeutic intervention favours at present diet and exercise prescriptions. In addition, if necessary, specific treatment of the metabolic disorders is required. In the treatment of insulin resistance, new promising drugs are likely to be used in the next future. In this regard, adipose tissue, once thought to function primarily as a passive depot for the storage of excess lipid, is now understood to play a much more active role in metabolic regulation, secreting a variety of metabolic hormones and actively functioning to prevent deleterious lipid accumulation in other tissues and to modulate the insulin resistance. Here, we review new advances in our understanding of mechanisms leading to insulin resistance and type 2 diabetes from the perspective of the role and interactions of recently identified adipocyte-specific chemical messengers, the adipocytokines, such as adiponectin, tumor necrosis factor-alpha, interleukin 6, and resistin.
Parties annexes
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