{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:01:46Z","timestamp":1791910906475,"version":"4.3.4"},"reference-count":54,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T00:00:00Z","timestamp":1557360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Dietary inorganic nitrate (NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>) lowers peripheral blood pressure (BP) in healthy volunteers, but lacks such effect in individuals with, or at risk of, type 2 diabetes mellitus (T2DM). Whilst this is commonly assumed to be a consequence of chronic hyperglycaemia\/hyperinsulinaemia, we hypothesized that acute physiological elevations in plasma [glucose]\/[insulin] blunt the haemodynamic responses to NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>, a pertinent question for carbohydrate\u2010rich Western diets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted an acute, randomized, placebo\u2010controlled, double\u2010blind, crossover study on the haemodynamic and metabolic effects of potassium nitrate (8 or 24\u00a0mmol KNO<jats:sub>3<\/jats:sub>) <jats:italic>vs<\/jats:italic>. potassium chloride (KCl; placebo) administered 1\u00a0hour prior to an oral glucose tolerance test in 33 healthy volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to placebo, there were no significant differences in systolic or diastolic BP (<jats:italic>P\u00a0=<\/jats:italic>\u00a00.27 and <jats:italic>P<\/jats:italic>\u00a0=\u00a00.30 on ANOVA, respectively) with KNO<jats:sub>3<\/jats:sub>, nor in pulse wave velocity or central systolic BP (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.99 and <jats:italic>P<\/jats:italic>\u00a0=\u00a00.54 on ANOVA, respectively). Whilst there were significant elevations from baseline for plasma [glucose] and [C\u2010peptide], no differences between interventions were observed. A significant increase in plasma [insulin] was observed with KNO<jats:sub>3<\/jats:sub> <jats:italic>vs<\/jats:italic>. KCl (<jats:italic>n<\/jats:italic>\u00a0=\u00a033; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.014 on ANOVA) with the effect driven by the high\u2010dose cohort (24\u00a0mmol, <jats:italic>n<\/jats:italic>\u00a0=\u00a013; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001 on ANOVA; at <jats:italic>T<\/jats:italic>\u00a0=\u00a00.75\u00a0h mean difference 210.4\u00a0pmol\/L (95% CI 28.5 to 392.3), <jats:italic>P<\/jats:italic>\u00a0=\u00a00.012).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In healthy adults, acute physiological elevations of plasma [glucose] and [insulin] result in a lack of BP\u2010lowering with dietary nitrate. The increase in plasma [insulin] without a corresponding change in [C\u2010peptide] or [glucose] suggests that high\u2010dose NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> decreases insulin clearance. A likely mechanism is via NO\u2010dependent inhibition of insulin\u2010degrading enzyme.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13913","type":"journal-article","created":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T17:24:38Z","timestamp":1551979478000},"page":"1443-1453","source":"Crossref","is-referenced-by-count":10,"title":["Acute interaction between oral glucose (75\u00a0g as Lucozade) and inorganic nitrate: Decreased insulin clearance, but lack of blood pressure\u2010lowering"],"prefix":"10.1111","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9359-6381","authenticated-orcid":false,"given":"Christopher N.","family":"Floyd","sequence":"first","affiliation":[{"name":"School of Cardiovascular Medicine and Sciences, Department of Clinical Pharmacology King's College London British Heart Foundation Centre  London UK"},{"name":"Biomedical Research Centre, Clinical Research Facility, Guy's and St Thomas' NHS Foundation Trust  London 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