Dysfunction of human subcutaneous FAT arterioles in obesity associated or not with Type 2 diabetes
Résumé
Objective: The present study aimed to examine the effects of obesity 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 signaling proteins. Research Design and Methods: Periumbilical subcutaneous adipose tissue was explanted at surgery, small arterioles (internal diameter 220 ± 40 mm) were dissected out and investigated by electron microscopy, myography and immunoblotting. Results: Compared to the subcutaneous arterioles of lean subjects, obesity activates the endothelium, enhances the accumulation of collagen within vascular wall and increases the sensitivity of adrenergic response; obesity also diminishes eNOS protein expression, NO production, endothelium-dependent and insulin-induced vasodilatation, as well as the protein expression of both insulin receptor substrates IRS-1 and IRS-2, and of the downstream molecules in insulin pathway, such as PI3-kinase, p-AKT and AKT. When obesity is joined with type 2 diabetes these changes are severely augmented. Conclusions: Obesity associated or not with type 2 diabetes alters human peri-umbilical adipose tissue arterioles in terms of structure, function and biochemsitry, including diminished eNOS expression and reduced levels of IRS-1, IRS-2, PI3-kinase and AKT in insulin-signaling pathway. Key words: arterioles, obesity, type 2 diabetes, insulin signaling, endothelial dysfunction.
Origine : Fichiers produits par l'(les) auteur(s)
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