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Artunc, F. ; Schleicher, E. ; Weigert, C. ; Fritsche, A. ; Stefan, N. ; Häring, H.-U.

The impact of insulin resistance on the kidney and vasculature.

Nat. Rev. Nephrol. 12, 721-737 (2016)
Postprint DOI PMC
Open Access Green
Insulin resistance is a systemic disorder that affects many organs and insulin-regulated pathways. The disorder is characterized by a reduced action of insulin despite increased insulin concentrations (hyperinsulinaemia). The effects of insulin on the kidney and vasculature differ in part from the effects on classical insulin target organs. Insulin causes vasodilation by enhancing endothelial nitric oxide production through activation of the phosphatidylinositol 3-kinase pathway. In insulin-resistant states, this pathway is impaired and the mitogen-activated protein kinase pathway stimulates vasoconstriction. The action of insulin on perivascular fat tissue and the subsequent effects on the vascular wall are not fully understood, but the hepatokine fetuin-A, which is released by fatty liver, might promote the proinflammatory effects of perivascular fat. The strong association of salt-sensitive arterial hypertension with insulin resistance indicates an involvement of the kidney in the insulin resistance syndrome. The insulin receptor is expressed on renal tubular cells and podocytes and insulin signalling has important roles in podocyte viability and tubular function. Renal sodium transport is preserved in insulin resistance and contributes to the salt-sensitivity of blood pressure in hyperinsulinaemia. Therapeutically, renal and vascular insulin resistance can be improved by an integrated holistic approach aimed at restoring overall insulin sensitivity and improving insulin signalling.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Korrespondenzautor
Schlagwörter Insulin signalling; Obesity; Podocytes; Type 2 diabetes; Perivascular Adipose-tissue; Glomerular-filtration-rate; Life-style Intervention; Nitric-oxide Synthase; Fetuin-a Levels; Alpha(2)-heremans-schmid Glycoprotein/fetuin-a; Metabolic Syndrome Subjects; Impaired Glucose-tolerance; Cotransporter 2 Inhibition; Nonalcoholic Fatty Liver
ISSN (print) / ISBN 1759-5061
e-ISSN 1759-507X
Zeitschrift Nature Reviews - Nephrology
Quellenangaben Band: 12, Heft: 12, Seiten: 721-737 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)