The involvement of aldosterone on vascular insulin resistance: implications in obesity and type 2 diabetes

Author(s)

Bruder-Nascimento, Thiago ^[1] ; da Silva, Marcondes A. B. ^[1] ; Tostes, Rita C. ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Review article
• Source: DIABETOLOGY & METABOLIC SYNDROME; v. 6, AUG 24 2014.
• Web of Science Citations: 15

Abstract

Aldosterone, a mineralocorticoid hormone produced at the adrenal glands, controls corporal hydroelectrolytic balance and, consequently, has a key role in blood pressure adjustments. Aldosterone also has direct effects in many organs, including the vasculature, leading to many cellular events that influence proliferation, migration, inflammation, redox balance and apoptosis. Aldosterone effects depend on its binding to mineralocorticoid receptors (MR). Aldosterone binding to MR triggers two pathways, the genomic pathway and the non-genomic pathway. In the vasculature e. g., activation of the non-genomic pathway by aldosterone induces rapid effects that involve activation of kinases, phosphatases, transcriptional factors and NAD(P) H oxidases. Aldosterone also plays a crucial role on systemic and vascular insulin resistance, i.e. the inability of a tissue to respond to insulin. Insulin has a critical role on cell function and vascular insulin resistance is considered an early contributor to vascular damage. Accordingly, aldosterone impairs insulin receptor (IR) signaling by altering the phosphatidylinositol 3-kinase (PI3K)/nitric oxide (NO) pathway and by inducing oxidative stress and crosstalk between the IR and the insulin-like growth factor-1 receptor (IGF-1R). This mini-review focuses on the relationship between aldosterone and vascular insulin resistance. Evidence indicating MR antagonists as therapeutic tools to minimize vascular injury associated with obesity and diabetes type 2 is also discussed. (AU)

• FAPESP's process: 11/01785-6 - Contribution of oxidative stress and NOXes to diabetes-associated vascular injury
• Grantee: Thiago Bruder Do Nascimento
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/52214-6 - Contribution of oxidative stress and NOXes to diabetes-associated vascular and renal injury
• Grantee: Rita de Cassia Aleixo Tostes Passaglia
• Support Opportunities: Regular Research Grants