title: Metabolic syndrome and hypertension: pathophysiology and molecular basis of insulin resistance.
abstract: Several recent studies indicate that type 2 diabetes, arterial hypertension, lipid disorders as well as visceral obesity are coronary risk factors which might belong to a syndrome which is caused by decreased insulin sensitivity with compensatory hyperinsulinaemia. More than 50% of patients with essential hypertension have some degree of insulin resistance, but in contrast to dyslipoproteinaemia and glucose intolerance the causal relation between insulin resistance and elevated arterial blood pressure appears not to be as evident. One explanation is that the link between blood pressure and insulin sensitivity might be mainly related to concomitant obesity. Accordingly, obesity can be associated with an increased activity of the sympathetic nervous system, elevated plasma levels of the vasoconstrictor endothelin-1, and decreased insulin-induced endothelium-dependent vasodilation. Furthermore, adipocytes can secrete vasogenic peptides, such as angiotensinogen. Since insulin resistance is a polygenic disorder, the two basic genetic approaches we follow is to identify genetic defects of insulin action in cells of patients with inherited syndromes of insulin resistance and to characterize molecular mechanisms of insulin regulated gene expression. The results show that insulin can affect the expression rate of various genes, e.g. involved in cholesterol and fatty acid metabolism, by modulating the activity of transcription factors coupled to the MAP kinase cascade and that a genetic postreceptor defect in these intracellular signaling pathways might have a pleiotropic effect on cell metabolism and clinical phenotype.
authors.affiliation: Klinik II und Poliklinik für Innere Medizin, Universität zu Köln, Cologne, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Müller-Wieland
authors.forename: J
authors.initials: J
authors.lastname: Kotzka
authors.forename: B
authors.initials: B
authors.lastname: Knebel
authors.forename: W
authors.initials: W
authors.lastname: Krone
mesh_terms: D002784:Cholesterol / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology*; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology*; D008659:Metabolic Diseases / Q000150:complications*; D009765:Obesity / Q000150:complications
chemical_list: D002784:Cholesterol