title: The impact of insulin resistance on the kidney and vasculature.
abstract: 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.
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.|German Center for Diabetes Research (DZD), Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.
authors.forename: Ferruh
authors.initials: F
authors.lastname: Artunc
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.|German Center for Diabetes Research (DZD), Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.
authors.forename: Erwin
authors.initials: E
authors.lastname: Schleicher
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.|German Center for Diabetes Research (DZD), Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.
authors.forename: Cora
authors.initials: C
authors.lastname: Weigert
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.|German Center for Diabetes Research (DZD), Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.|German Center for Diabetes Research (DZD), Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Stefan
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.|German Center for Diabetes Research (DZD), Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
mesh_terms: D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D004727:Endothelium / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism*; D007684:Kidney Tubules / Q000502:physiology; D024821:Metabolic Syndrome / Q000628:therapy; D020239:Receptor Cross-Talk; D015398:Signal Transduction; D017673:Sodium Chloride, Dietary
chemical_list: D017673:Sodium Chloride, Dietary