title: Dysfunction of human subcutaneous fat arterioles in obesity alone or obesity associated with Type 2 diabetes.
abstract: The aim of the present study was to examine the effects of obesity alone and obesity associated with Type 2 diabetes on the structure, vascular reactivity and response to insulin of isolated human subcutaneous fat arterioles; these effects were correlated with the expression of insulin signalling proteins. Periumbilical subcutaneous adipose tissue was explanted during surgery, small arterioles (internal diameter 220 ± 40 μm) were dissected out and investigated by electron microscopy, myography and immunoblotting. Compared with the subcutaneous arterioles of lean subjects, obesity activated the endothelium, enhanced the accumulation of collagen within vascular wall and increased the sensitivity of adrenergic response; obesity also diminished eNOS (endothelial NO synthase) protein expression, NO production, and endothelium-dependent and insulin-induced vasodilatation, as well as the protein expression of both IRS (insulin receptor substrates)-1 and IRS-2 and of the downstream molecules in the insulin signalling pathway, such as PI3K (phosphoinositide 3-kinase), phospho-Akt and Akt. When obesity was associated with Type 2 diabetes, these changes were significantly augmented. In conclusion, obesity alone or obesity associated with Type 2 diabetes alters human periumbilical adipose tissue arterioles in terms of structure, function and biochemsitry, including diminished eNOS expression and reduced levels of IRS-1, IRS-2, PI3K and Akt in the insulin signalling pathway.
authors.affiliation: Petru Poni Institute of Macromolecular Chemistry, Iasi, Romania. adriana.georgescu@icbp.ro
authors.forename: Adriana
authors.initials: A
authors.lastname: Georgescu
authors.forename: Doina
authors.initials: D
authors.lastname: Popov
authors.forename: Anamaria
authors.initials: A
authors.lastname: Constantin
authors.forename: Miruna
authors.initials: M
authors.lastname: Nemecz
authors.forename: Nicoleta
authors.initials: N
authors.lastname: Alexandru
authors.forename: Daniel
authors.initials: D
authors.lastname: Cochior
authors.forename: Aura
authors.initials: A
authors.lastname: Tudor
mesh_terms: D000328:Adult; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009213:Myography / Q000379:methods; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D050151:Subcutaneous Fat / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D007328:Insulin; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D009638:Norepinephrine