{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:50:14Z","timestamp":1791435014331,"version":"4.3.3"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rembrandt Grant"},{"name":"NWO VICI","award":["09150182010020"],"award-info":[{"award-number":["09150182010020"]}]},{"DOI":"10.13039\/100010663","name":"ERC","doi-asserted-by":"publisher","award":["101141346"],"award-info":[{"award-number":["101141346"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dutch Kidney and Dutch Diabetes Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>In healthy individuals, oral sodium loading induces more rapid natriuresis than intravenous administration, suggesting a gut-kidney feed-forward mechanism. Whether this physiological response is impaired in type 2 diabetes (T2D), and whether pharmacological glucagon-like peptide-1 receptor agonism can restore it, remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We conducted a mechanistic, randomized, double-blind, placebo-controlled cross-over trial, in men with T2D. Participants adhered to a standardized sodium intake (&amp;lt;90 mmol\/day) for 7 days before each study visit. Each participant underwent three experimental conditions in random order: (1) intravenous sodium loading (ISL), (2) oral sodium loading with placebo (OSL-placebo) infusion, and (3) OSL with concomitant exenatide infusion (OSL-exenatide). Each sodium load contained 154 mmol sodium. The primary endpoint was cumulative urinary sodium excretion over 24-h. Secondary endpoints included early natriuresis, fractional sodium excretion, ambulatory blood pressure, extracellular volume, and measured glomerular filtration rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eleven men with T2D (mean age 60\u00a0\u00b1\u00a04.7 years, BMI 31.9\u00a0\u00b1\u00a03.9 kg\/m2, HbA1c 7.5\u00a0\u00b1\u00a00.9%, systolic blood pressure 127\u00a0\u00b1\u00a022 mmHg) completed the study. Median cumulative 24 h sodium excretion did not differ significantly between ISL (105; IQR 55\u2013156 mmol), OSL-placebo (101; 71\u2013134 mmol), or OSL-exenatide (100; 63\u2013123 mmol). Early natriuretic responses and fractional sodium excretion were similar across interventions. Daytime and nighttime blood pressure did not differ between interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In contrast to observations in healthy individuals, OSL did not result in elevated natriuresis compared with ISL in T2D, consistent with impaired gut-kidney feed-forward regulation. Acute GLP-1R-activation with exenatide did not restore this response, suggesting additional entero-renal pathways mediate postprandial natriuretic regulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ckj\/sfag315","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:49:10Z","timestamp":1789127350000},"source":"Crossref","is-referenced-by-count":0,"title":["Gut-kidney signaling is impaired in individuals with type 2 diabetes"],"prefix":"10.1093","volume":"19","author":[{"given":"Charlotte M","family":"Mosterd","sequence":"first","affiliation":[{"name":"Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center , Amsterdam ,","place":["The Netherlands"]},{"name":"Department of Vascular Medicine, Amsterdam UMC , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1128-2482","authenticated-orcid":false,"given":"Britt E","family":"Wever","sequence":"additional","affiliation":[{"name":"Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center , Amsterdam ,","place":["The Netherlands"]},{"name":"Department of Vascular Medicine, Amsterdam UMC , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel J B","family":"van\u00a0Baar","sequence":"additional","affiliation":[{"name":"Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel H A","family":"Muskiet","sequence":"additional","affiliation":[{"name":"Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center , Amsterdam ,","place":["The Netherlands"]},{"name":"Department of Medicine, Division of Endocrinology, Leiden University Medical Center , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0943-4393","authenticated-orcid":false,"given":"Bert-Jan H","family":"van\u00a0den\u00a0Born","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam UMC , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1926-7659","authenticated-orcid":false,"given":"Max","family":"Nieuwdorp","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam UMC , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daan J","family":"Touw","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Rijksuniversiteit Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8738-3571","authenticated-orcid":false,"given":"Ewout J","family":"Hoorn","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liffert","family":"Vogt","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Amsterdam UMC , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00ebl H","family":"van\u00a0Raalte","sequence":"additional","affiliation":[{"name":"Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center , Amsterdam ,","place":["The Netherlands"]},{"name":"Department of Vascular Medicine, Amsterdam UMC , Amsterdam ,","place":["The 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