Blockade of endothelin-1 receptor type B ameliorates glucose intolerance and insulin resistance in a mouse model of obstructive sleep apnea

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F18%3A43916728" target="_blank" >RIV/00216208:11120/18:43916728 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.3389/fendo.2018.00280" target="_blank" >https://doi.org/10.3389/fendo.2018.00280</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fendo.2018.00280" target="_blank" >10.3389/fendo.2018.00280</a>

Result language

angličtina

Original language name

Blockade of endothelin-1 receptor type B ameliorates glucose intolerance and insulin resistance in a mouse model of obstructive sleep apnea

Original language description

Obstructive sleep apnea (OSA) is associated with insulin resistance (IR) and glucose intolerance. Elevated endothelin-1 (ET-1) levels have been observed in OSA patients and in mice exposed to intermittent hypoxia (IH). We examined whether pharmacological blockade of type A and type B ET-1 receptors (ETA and ETB) would ameliorate glucose intolerance and IR in mice exposed to IH. Subcutaneously implanted pumps delivered BQ-123 (ETA antagonist; 200 nmol/kg/day), BQ-788 (ETB antagonist; 200 nmol/kg/day) or vehicle (saline or propyleneglycol [PG]) for 14 days in C57BL6/J mice (10/group). During treatment, mice were exposed to IH (decreasing the FiO2 from 20.9% to 6%, 60/h) or intermittent air (IA). After IH or IA exposure, insulin (0.5 IU/kg) or glucose (1 mg/kg) was injected intraperitoneally and plasma glucose determined after injection and area under glucose curve (AUC) was calculated. Fourteen-day IH increased fasting glucose levels (122 +- 7 vs. 157 +- 8 mg/dL, PG: 118 +- 6 vs. 139 +- 8; both p &lt; 0.05) and impaired glucose tolerance (AUCglucose: 19,249 +- 1105 vs. 29,124 +- 1444, PG AUCglucose: 18,066 +- 947 vs. 25,135 +- 797; both p &lt; 0.05) in vehicle-treated animals. IH-induced impairments in glucose tolerance were partially ameliorated with BQ-788 treatment (AUCglucose: 21,969 +- 662; p &lt; 0.05). Fourteen-day IH also induced IR (AUCglucose: 7185 +- 401 vs. 8699 +- 401; p &lt; 0.05). Treatment with BQ-788 decreased IR under IA (AUCglucose: 5281 +- 401, p &lt; 0.05) and reduced worsening of IR with IH (AUCglucose: 7302 +- 401, p &lt; 0.05). There was no effect of BQ-123 on IH-induced impairments in glucose tolerance or IR. Our results suggest that ET-1 plays a role in IH-induced impairments in glucose homeostasis.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Endocrinology

ISSN

1664-2392

e-ISSN

—

Volume of the periodical

9

Issue of the periodical within the volume

May

Country of publishing house

CH - SWITZERLAND

Number of pages

10

Pages from-to

"Article 280"

UT code for WoS article

000433313800001

EID of the result in the Scopus database

2-s2.0-85047659427