title: [Insulin and angiotensin II signaling pathways cross-talk: implications with the association between diabetes mellitus, arterial hypertension and cardiovascular disease].
abstract: Insulin (Ins) and angiotensin II (AII) play pivotal roles in the control of two vital and closely related systems: the metabolic and the circulatory, respectively. A failure in the proper action of each of these hormones results, to a variable degree, in the development of two highly prevalent and commonly overlapping diseases--diabetes mellitus (DM) and hypertension (AH). In recent years, a series of studies has revealed a tight connection between the signal transduction pathways that mediate Ins and AII actions in target tissues. This molecular cross-talk occurs at multiple levels and plays an important role in phenomena that range from the action of anti-hypertensive drugs to cardiac hypertrophy and energy acquisition by the heart. At the extracellular level, the angiotensin-converting enzyme controls AII synthesis but also interferes with Ins signaling through the proper regulation of AII and the accumulation of bradykinin. At an early intracellular level, AII, acting through JAK-2/IRS-1/PI3-kinase, JNK and ERK, may induce the serine phosphorylation and inhibition of key elements of the Ins-signaling pathway. Finally, by inducing the expression of the regulatory protein SOCS-3, AII may impose a late control on the Ins signal. This review will focus on the main advances obtained in this field and will discuss the implications of this molecular cross-talk in the common clinical association between DM and AH.
authors.affiliation: Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, SP, Brazil.
authors.forename: Marco A de
authors.initials: MA
authors.lastname: Carvalho-Filho
authors.forename: José Barreto C
authors.initials: JB
authors.lastname: Carvalheira
authors.forename: Lício Augusto
authors.initials: LA
authors.lastname: Velloso
authors.forename: Mario José Abdalla
authors.initials: MJ
authors.lastname: Saad
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D003920:Diabetes Mellitus / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology
chemical_list: D007328:Insulin; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000804:Angiotensin II