Department of Medicine-Endocrinology and Metabolism, University of Missouri School of Medicine, Columbia, MO 65212, USA.
Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO 65212, USA.
Int J Mol Sci. 2022 Aug 11;23(16):8954. doi: 10.3390/ijms23168954.
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.
全身胰岛素抵抗的特征是胰岛素代谢信号转导减少和葡萄糖耐量降低。盐皮质激素受体（MRs）是激素醛固酮的主要受体，在调节肾脏钠处理和血压方面发挥着重要作用。最近的研究表明，MRs 也存在于肾脏以外的组织中，包括血管内皮细胞、平滑肌细胞、成纤维细胞、血管周围脂肪组织和免疫细胞。风险因素，包括盐摄入过多/盐敏感性、高血压和肥胖，可导致血管 MRs 的激活，从而促进炎症、氧化应激、重塑和纤维化，以及心血管僵硬和微循环损伤。这些病理生理变化与胰岛素启动适当细胞内信号事件的能力降低有关，导致微循环中葡萄糖摄取减少和相关的血管胰岛素抵抗。因此，MR 激活的药理学抑制为改善血管功能、葡萄糖摄取和血管胰岛素敏感性提供了一种潜在的治疗选择。本综述强调了最近的实验和临床数据，这些数据支持异常 MR 激活对血管胰岛素抵抗和功能障碍发展的贡献。
