title: Effects of aldosterone on insulin sensitivity and secretion.
abstract: Dr. Conn originally reported an increased risk of diabetes in patients with hyperaldosteronism in the 1950s, although the mechanism remains unclear. Aldosterone-induced hypokalemia was initially described to impair glucose tolerance by impairing insulin secretion. Correction of hypokalemia by potassium supplementation only partially restored insulin secretion and glucose tolerance, however. Aldosterone also impairs glucose-stimulated insulin secretion in isolated pancreatic islets via reactive oxygen species in a mineralocorticoid receptor-independent manner. Aldosterone-induced mineralocorticoid receptor activation also impairs insulin sensitivity in adipocytes and skeletal muscle. Aldosterone may produce insulin resistance secondarily by altering potassium, increasing inflammatory cytokines, and reducing beneficial adipokines such as adiponectin. Renin-angiotensin system antagonists reduce circulating aldosterone concentrations and also the risk of type 2 diabetes in clinical trials. These data suggest that primary and secondary hyperaldosteronism may contribute to worsening glucose tolerance by impairing insulin sensitivity or insulin secretion in humans. Future studies should define the effects of MR antagonists and aldosterone on insulin secretion and sensitivity in humans.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, United States. Electronic address: James.Luther@Vanderbilt.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Luther
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008954:Models, Biological
chemical_list: D007328:Insulin; D000450:Aldosterone
keywords: Aldosterone; Diabetes; Hypertension; Insulin secretion; Insulin sensitivity; Mineralocorticoid receptor