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Intermittent Hypoxia‐Induced Insulin Resistance Is Ameliorated By Endothelin‐1 Receptor Type B Antagonist
Author(s) -
Polak Jan,
Punjabi Naresh M.,
Shimoda Larissa A.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.938.10
Subject(s) - medicine , intermittent hypoxia , endocrinology , insulin resistance , antagonist , endothelin receptor , glucose homeostasis , homeostasis , obstructive sleep apnea , endothelin 1 , chemistry , receptor antagonist , insulin , receptor
Obstructive sleep apnea (OSA) is associated with decreased insulin sensitivity (IS). Endothelin‐1 (ET‐1) impairs insulin signaling and alters glucose homeostasis. Patients with OSA and mice exposed to intermittent hypoxia (IH) have elevated ET‐1 levels. We examined whether blockade of ET‐1 receptors type A (ETA) and type B (ETB) ameliorates worsening of IS under IH in mice. Subcutaneously implanted pumps delivered BQ‐123 (ETA antagonist; 200 nmol/kg/d), BQ‐788 (ETB antagonist; 200 nmol/kg/d) or vehicle (saline or propyleneglycol [PG]) for 14 days in C57BL6/J mice (10/group). During treatment, mice were exposed to IH or intermittent air (IA). IH was induced by decreasing the FiO2 from 20.9% to 6% (60/hr). After IH or IA exposure, insulin was injected intraperitoneally (0.5 IU/kg) and plasma glucose determined at 0, 10, 20, 30, 40, 50, 60, 90 and 120 minutes after injection. IS was assessed as the area under glucose curve (AUC). 14‐days of IH impaired IS (AUCglucose: 7185±401 vs 8699±401; p<0.05). Treatment with BQ‐788 improved IS under IA (AUCglucose: 5281±401, p<0.05) and prevented worsening of IS with IH (AUCglucose: 7302±401, p<0.05). While BQ‐123 treatment also improved IS under IA (AUCglucose: 6557±545, p=0.05), no effect was observed under IH (AUC: 9989±599, p>;0.05). Treatment with selective ETB receptor antagonist prevented worsening of IS with IH, suggesting that ET‐1 plays a role in glucose homeostasis.