Administration of tauroursodeoxycholic acid prevents endothelial dysfunction caused by an oral glucose load

Lauren K. Walsh, Robert M. Restaino, Martha Neuringer, Camila Manrique, Jaume Padilla

    Research output: Contribution to journalArticle

    16 Scopus citations

    Abstract

    Postprandial hyperglycaemia leads to a transient impairment in endothelial function; however, the mechanisms remain largely unknown. Previous work in cell culture models demonstrate that high glucose results in endoplasmic reticulum (ER) stress and, in animal studies, ER stress has been implicated as a cause of endothelial dysfunction. In the present study, we tested the hypothesis that acute oral administration of tauroursodeoxycholic acid (TUDCA, 1500 mg), a chemical chaperone known to alleviate ER stress, would prevent hyperglycaemia-induced endothelial dysfunction. In 12 young healthy subjects (seven men, five women), brachial artery flow-mediated dilation (FMD) was assessed at baseline, and at 60 and 120 min after an oral glucose challenge. Subjects were tested on two separate visits in a single-blind randomized cross-over design: after oral ingestion of TUDCA or placebo capsules. FMD was reduced from baseline during hyperglycaemia under the placebo condition (-32% at 60 min and -28% at 120 min post oral glucose load; P<0.05 from baseline) but not under the TUDCA condition (-4% at 60 min and +0.3% at 120 min post oral glucose load; P>0.05 from baseline). Postprandial plasma glucose and insulin were not altered by TUDCA ingestion. Plasma oxidative stress markers 3-nitrotyrosine and thiobarbituric acid reactive substance (TBARS) remained unaltered throughout the oral glucose challenge in both conditions. These results suggest that hyperglycaemia-induced endothelial dysfunction can be mitigated by oral administration of TUDCA, thus supporting the hypothesis that ER stress may contribute to endothelial dysfunction during postprandial hyperglycaemia.

    Original languageEnglish (US)
    Pages (from-to)1881-1888
    Number of pages8
    JournalClinical science (London, England : 1979)
    Volume130
    Issue number21
    DOIs
    Publication statusPublished - Nov 1 2016

      Fingerprint

    Keywords

    • endothelial function
    • ER stress
    • postprandial hyperglycaemia
    • tauroursodeoxycholic acid (TUDCA)

    ASJC Scopus subject areas

    • Medicine(all)

    Cite this