Pulmonary vascular effect of insulin in a rodent model of pulmonary arterial hypertension.

Autor: Trammell AW; 1 Division of Allergy, Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA, USA.; 2 Division of Allergy, Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA., Talati M; 2 Division of Allergy, Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA., Blackwell TR; 2 Division of Allergy, Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA., Fortune NL; 2 Division of Allergy, Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA., Niswender KD; 3 Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA., Fessel JP; 2 Division of Allergy, Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA., Newman JH; 2 Division of Allergy, Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA., West JD; 2 Division of Allergy, Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA., Hemnes AR; 2 Division of Allergy, Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Jazyk: angličtina
Zdroj: Pulmonary circulation [Pulm Circ] 2017 Jul-Sep; Vol. 7 (3), pp. 624-634. Date of Electronic Publication: 2017 Aug 07.
DOI: 10.1086/689908
Abstrakt: Pulmonary arterial hypertension (PAH) is associated with metabolic derangements including insulin resistance, although their effects on the cardiopulmonary disease are unclear. We hypothesized that insulin resistance promotes pulmonary hypertension (PH) development and mutations in type 2 bone morphogenetic protein receptor (BMPR2) cause cellular insulin resistance. Using a BMPR2 transgenic murine model of PAH and two models of inducible diabetes mellitus, we explored the impact of hyperglycemia and/or hyperinsulinemia on development and severity of PH. We assessed insulin signaling and insulin-mediated glucose uptake in human endothelial cells with and without mutations in BMPR2. PH developed in control mice fed a Western diet and PH in BMPR2 mutant mice was increased by Western diet. Pulmonary artery pressure correlated strongly with fasting plasma insulin but not glucose. Reactive oxygen species were increased in lungs of insulin-resistant animals. BMPR2 mutation impaired insulin-mediated endothelial glucose uptake via reduced glucose transporter translocation despite intact insulin signaling. Experimental hyperinsulinemia is strongly associated with PH in both control and BMPR2-mutant mice, though to a greater degree in those with BMPR2 mutation. Human pulmonary endothelial cells with BMPR2 mutation have evidence of reduced glucose uptake due to impaired glucose transporter translocation. These experiments support a role for hyperinsulinemia in pulmonary vascular disease.
Databáze: MEDLINE
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