title: Insulin down-regulates TRAIL expression in vascular smooth muscle cells both in vivo and in vitro.
abstract: To dissect the effect of hyperinsulinemia versus hyperglycemia on TNF-related apoptosis inducing ligand (TRAIL) expression in the macrovascular district, we measured TRAIL mRNA and protein in four groups of animals: streptozotocin (SZT)-induced diabetic rats, vehicle-treated control animals, diabetic rats treated with insulin and non-diabetic rats treated with insulin. While the aortas of diabetic rats did not show significant differences in TRAIL expression with respect to vehicle-treated control animals, the aortas of both diabetic and non-diabetic rats treated in vivo for 16 days with insulin showed a significant decrease in TRAIL expression with respect to either diabetic and control rats. Moreover, in vitro treatment of both rat and human vascular smooth muscle cells (VSMC) with insulin induced the down-regulation of TRAIL protein. While the addition of recombinant TRAIL to rat VSMC promoted the dose-dependent release of bioactive nitric oxide (NO), this effect was significantly counteracted by pre-exposure of VSMC to insulin. These findings suggest that TRAIL might act as an endogenous regulator of the vascular tone and that chronic elevation of insulin might contribute to the vascular abnormalities characterizing type-2 diabetes mellitus by down-regulating TRAIL expression and activity.
authors.affiliation: Department of Normal Human Morphology, University of Trieste, Trieste, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Corallini
authors.forename: Claudio
authors.initials: C
authors.lastname: Celeghini
authors.forename: Clara
authors.initials: C
authors.lastname: Rizzardi
authors.forename: Assunta
authors.initials: A
authors.lastname: Pandolfi
authors.forename: Sara
authors.initials: S
authors.lastname: Di Silvestre
authors.forename: Mauro
authors.initials: M
authors.lastname: Vaccarezza
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zauli
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008840:Microfilament Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D007328:Insulin; D008840:Microfilament Proteins; D009569:Nitric Oxide; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; D000096985:Calponins