Mineralocorticoid Receptor Activation in Vascular Insulin Resistance and Dysfunction

Systemic insulin resistance is characterized by reduced insulin metabolic signaling and glucose intolerance. Mineralocorticoid receptors (MRs), the principal receptors for the hormone aldosterone, play an important role in regulating renal sodium handling and blood pressure. Recent studies suggest that MRs also exist in tissues outside the kidney, including vascular endothelial cells, smooth muscle cells, fibroblasts, perivascular adipose tissue, and immune cells. Risk factors, including excessive salt intake/salt sensitivity, hypertension, and obesity, can lead to the activation of vascular MRs to promote inflammation, oxidative stress, remodeling, and fibrosis, as well as cardiovascular stiffening and microcirculatory impairment. These pathophysiological changes are associated with a diminished ability of insulin to initiate appropriate intracellular signaling events, resulting in a reduced glucose uptake within the microcirculation and related vascular insulin resistance. Therefore, the pharmacological inhibition of MR activation provides a potential therapeutic option for improving vascular function, glucose uptake, and vascular insulin sensitivity. This review highlights recent experimental and clinical data that support the contribution of abnormal MR activation to the development of vascular insulin resistance and dysfunction.

Automated summary

Systemic insulin resistance is characterized by reduced insulin signaling and glucose intolerance. Mineralocorticoid receptors (MRs) play a role in regulating renal sodium handling and blood pressure, and recent studies show their presence in tissues outside the kidney. Risk factors like excessive salt intake, hypertension, and obesity can activate vascular MRs, leading to inflammation, oxidative stress, remodeling, fibrosis, cardiovascular stiffening, and microcirculatory impairment. These changes contribute to vascular insulin resistance and reduced glucose uptake. Pharmacological inhibition of MR activation could potentially improve vascular function, glucose uptake, and insulin sensitivity.