Mineralocorticoid receptors in the pathogenesis of insulin resistance and related disorders: from basic studies to clinical disease.

Abstract	Aldosterone is a steroid hormone that regulates blood pressure and cardiovascular function by acting on renal and vascular mineralocorticoid receptors (MRs) to promote sodium retention and modulate endothelial function. Indeed, MRs are expressed in endothelial cells, vascular smooth muscle cells, adipocytes, immune cells, skeletal muscle cells, and cardiomyocytes. Excessive aldosterone and associated MR activation impair insulin secretion, insulin metabolic signaling to promote development of diabetes, and the related cardiometabolic syndrome. These adverse effects of aldosterone are mediated, in part, via increased inflammation, oxidative stress, dyslipidemia, and ectopic fat deposition. Therefore, inhibition of MR activation may have a beneficial effect in prevention of impaired insulin metabolic signaling, type 2 diabetes, and cardiometabolic disorders. This review highlights findings from the recent surge in research regarding MR-related cardiometabolic disorders as well as our contemporary understanding of the detrimental effects of excess MR activation on insulin metabolic signaling.
Authors	Guanghong Jia, Warren Lockette, James R Sowers
Journal	American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 320 Issue 3 Pg. R276-R286 (03 01 2021) ISSN: 1522-1490 [Electronic] United States
PMID	33438511 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review)
Chemical References	Blood Glucose Hypoglycemic Agents Mineralocorticoid Receptor Antagonists Receptors, Mineralocorticoid Aldosterone
Topics	Aldosterone (metabolism) Animals Blood Glucose (metabolism) Diabetes Mellitus, Type 2 (drug therapy, metabolism, physiopathology) Humans Hypoglycemic Agents (pharmacology) Insulin Resistance Lipid Metabolism Metabolic Syndrome (drug therapy, metabolism, physiopathology) Mineralocorticoid Receptor Antagonists (pharmacology) Oxidative Stress Receptors, Mineralocorticoid (drug effects, metabolism) Signal Transduction

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