Abstract 276: Chemerin Decreases Vascular Insulin Signaling.
Proinflammatory adipokines are key mediators of insulin resistance. The adipokine chemerin influences major aspects of the metabolic syndrome, including adipogenesis and glucose homeostasis in adipocytes and skeletal muscle cells. Amongst its many actions insulin also influences vascular function. Considering that chemerin impairs vascular reactivity, and that its effects in the vascular actions of insulin have not been investigated, we postulate that chemerin decreases vascular responses to insulin by reducing PI3K/Akt signaling. Isometric force was recorded in mesenteric arteries from C57Bl6 mice, incubated with chemerin (0.5 ng/mL, 1 h) or vehicle (veh). Chemerin decreased relaxation responses to insulin (0.1 - 3000 ng/mL, pD2: chemerin: 94.5±0.1 vs. veh: 23.6±0,1) and to ACh (pD2: 5.2±0.1 vs. veh 6.6±0.1). Chemerin effects on insulin-induced vasodilatation were reverted by the PI3K activator YS-49 (pD2: veh= 23.0±0.1; chem= 108.5±0.1, YS-49+chem= 28.5±0.1) and by inhibitors of p38 (pD2: veh= 23.0±0.1; chem= 108.5±0.1, SB203580+chem= 27.1±0.1) and ERK1/2 (pD2: veh= 24.6±0.1; chem= 112.0±0.1, PD98059+chem= 25.4±0.1). Chemerin also decreased PI3K [arbitrary units (a.u.): 0.8±0.1 vs. veh 1.1±0.1) and Akt (a.u.: 0.8±0.1 vs. veh 1.2±0.1) phosphorylation in cultured vascular smooth muscle cells (VSMCs). Furthermore, chemerin inhibited insulin-stimulated glucose uptake by VSMCs ([3H] 2-deoxy-glucose (2DG) uptake, counts per minute: 5668±729.0 vs. veh 9923±662.7). In conclusion, chemerin decreases insulin vascular responses by reducing PI3K/Akt signaling and by activating the MAPK pathway. These results suggest that chemerin may be involved in the pathogenesis of vascular insulin resistance. Our study may contribute to a better understanding of the role of factors released by the adipose tissue on insulin vascular responsiveness and, consequently, on the vascular dysfunction in obesity and obesity-associated diseases. Financial Support: FAPESP.
Author Disclosures: K.B. Neves: None. N.S. Lobato: None. R.A.M. Lopes: None. F.L. Mestriner: None. A. Oliveira: None. R.C. Tostes: None.
- © 2014 by American Heart Association, Inc.