title: Molecular mechanisms involved in obesity-associated insulin resistance: therapeutical approach.
abstract: Insulin resistance is an important contributor to the pathogenesis of T2D and obesity is a risk factor for its development. It has been demonstrated that these obesity-related metabolic disorders are associated with a state of chronic low-intensity inflammation. Several mediators released from adipocytes and macrophages, such as the pro-inflammatory cytokines TNF-alpha and IL-6, have been suggested to impair insulin action in peripheral tissues, including fat and skeletal muscle. Such insulin resistance can initially be compensated by increased insulin secretion, but the prolonged presence of the hormone is detrimental for insulin sensitivity. Stress and pro-inflammatory kinases as well as more recent players, phosphatases, seem to be involved in the molecular mechanisms by which pro-inflammatory cytokines and hyperinsulinemia disrupt insulin signalling at the level of IRSs. Pharmacological approaches, such as treatment with PPAR and LXR agonists, overcome such insulin resistance, exerting anti-inflammatory properties as well as controlling the expression of cytokines with tissular specificity.
authors: Departamento de Bioquimica y Biologia Molecular II, Facultad de Farmacia, Universidad Complutense, 28040-Madrid, Spain. soferve@farm.ucm.es
authors: Sonia
authors: S
authors: Fernández-Veledo
authors: Iria
authors: I
authors: Nieto-Vazquez
authors: Rocio
authors: R
authors: Vila-Bedmar
authors: Lucia
authors: L
authors: Garcia-Guerra
authors: Maria
authors: M
authors: Alonso-Chamorro
authors: Margarita
authors: M
authors: Lorenzo
mesh_terms: D000273:Adipose Tissue / Q000503:physiopathology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000502:physiology; D007515:Islets of Langerhans / Q000503:physiopathology; D009765:Obesity / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha