La contribution du récepteur B1 des kinines dans les complications diabétiques chez le rat traité au glucose, un modèle de résistance à l'insuline
Kinins act on two G-protein-coupled receptors, denoted as B1 and B2, and play an important role in cardiovascular regulation, nociception and inflammation. We have considered the hypothesis that kinin B1 receptor is upregulated and involved in diabetic complications, notably hypertension, pain sensory neuropathy, the oxidative stress in the vasculature, vascular inflammation, insulin resistance and obesity in rats treated for 8 or 12 weeks with D-glucose (10% of glucose in their drinking water). In this model of insulin resistance, we assessed the effects of one-week treatment with SSR240612 (10 mg/kg/day), a selective kinin B1 receptor antagonist. Data show that SSR240612 reverses high blood pressure, tactile and cold allodynia, the production of oxidative stress (superoxyde anion) in the aorta, the overexpression of iNOS, IL-1β, macrophage (CD68, CD11), ICAM-1, E-selectine, MIF and B1R in the aorta and iNOS, IL-1β, TNF-α and macrophage (CD68) in adipocytes. Moreover, SSR240612 reverses insulin resistance, plasma fatty acids composition changes and body and tissue fat gain.  These data support a key role for kinins in diabetic complications in a rat model of insulin resistance and suggest that kinin B1 receptor is a promising therapeutic target in diabetes and obesity.
allodynia type 2 diabetes arterial hypertension inflammation inflammation kinin receptors obesity insulin resistance