Gut-kidney signaling is impaired in individuals with type 2 diabetes.

Authors

Charlotte M Mosterd, Britt E Wever, Michiel J B van Baar, Marcel H A Muskiet, Bert-Jan H van den Born, Max Nieuwdorp, Daan J Touw, Ewout J Hoorn, Liffert Vogt, Daniël H van Raalte

Published in

Clinical kidney journal. Volume 19. Issue 10. Pages sfag315. Epub Sep 12, 2026.

Abstract

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.
We conducted a mechanistic, randomized, double-blind, placebo-controlled cross-over trial, in men with T2D. Participants adhered to a standardized sodium intake (<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.
Eleven men with T2D (mean age 60 ± 4.7 years, BMI 31.9 ± 3.9 kg/m², HbA1c 7.5 ± 0.9%, systolic blood pressure 127 ± 22 mmHg) completed the study. Median cumulative 24 h sodium excretion did not differ significantly between ISL (105; IQR 55-156 mmol), OSL-placebo (101; 71-134 mmol), or OSL-exenatide (100; 63-123 mmol). Early natriuretic responses and fractional sodium excretion were similar across interventions. Daytime and nighttime blood pressure did not differ between interventions.
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.

PMID:
42851342
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

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