Anti-inflammatory and anti-proliferative action of adiponectin mediated by insulin signaling cascade in human vascular s
- PDF / 1,581,724 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 22 Downloads / 131 Views
ORIGINAL ARTICLE
Anti‑inflammatory and anti‑proliferative action of adiponectin mediated by insulin signaling cascade in human vascular smooth muscle cells Eugenio Cersosimo1 · Xiaojing Xu1 · Tomoko Terasawa1 · Lily Q. Dong2 Received: 10 February 2020 / Accepted: 2 August 2020 © Springer Nature B.V. 2020
Abstract After confirmation of the presence of adiponectin (ADPN) receptors and intra-cellular binding proteins in coronary artery smooth muscle cells (VSMC), we tested the hypotheses that, in acute insulin resistance: (i) the activation/inactivation of metabolic and mitogenic insulin signaling pathways are inversely affected by ADPN and, (ii) changes in VSMC migration/ proliferation rates correlate with signal activity/inactivity. In primary cultures of VSMC exposed to high glucose and palmitate plus insulin, the expression of PI-3 kinase (Akt and m-TOR), MAP-Kinase (Erk and p-38) molecules, and inflammatory markers (TLR-4 and IkB-α) were assessed with Western blot, in the absence/presence of AdipoRon (AR). Migration and proliferation rates were measured in similar experimental conditions. There were decreases of ~ 25% (p-Akt) and 40–60% (p-mTOR) expressions with high glucose/palmitate, which reversed when AR was added were. Elevations in p-Erk and p-p38 expressions were obliterated by AR. Although, no changes were detected with high glucose and palmitate, when AR was added, a decline in inflammatory activity was substantiated by a ~ 50% decrease in TLR-4 and 40–60% increase in IkBα expression. Functional assays showed 10–20% rise in VSMC proliferation with high glucose and palmitate, but addition of AR lead to 15–25% decline. The degree of VSMC migration was reduced with AR addition by ~ 15%, ~ 35% and 55%, in VSMC exposed to 5 mM, 25 mM glucose and 25 mM + 200 µM palmitate, respectively. Changes in intracellular molecular messaging in experiments mimicking acute insulin resistance suggest that anti-inflammatory and anti-atherogenic actions of ADPN in VSMC are mediated via insulin signaling pathways. Keywords Adiponectin · Insulin signaling · Arterial smooth muscle cells · Cell migration & proliferation · Inflammation · Hyperinsulinemia · Insulin resistance
Introduction The high prevalence and early onset with rapid progression of atherosclerotic cardiovascular disease (ASCVD) in people with the cardio-metabolic syndrome (a combination of Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05707-w) contains supplementary material, which is available to authorized users. * Eugenio Cersosimo [email protected] 1
Department of Medicine, Division of Diabetes and the Texas Diabetes Institute, University Health System, 7703 Floyd Curl Drive MS 7886, San Antonio, TX 78229‑3900, USA
Department of Cell Systems and Anatomy, University of Texas Health San Antonio, San Antonio, TX, USA
2
glucose intolerance, hypertension, obesity and dyslipidemia) are well documented [1]. Having type 2 diabetes (T2DM) increases even further the risk of developing car
Data Loading...
