Increased oral sodium chloride intake in humans amplifies selectively postprandial GLP-1 but not GIP, CCK, and gastrin in plasma.

Ali Asmar,Charlotte M Sorensen,Cedric Moro,Meena Asmar,Peter Hovind,Jens J Holst,Sten Madsbad,Bolette Hartmann,Lene Simonsen,Per K Cramon,Boye L Jensen,Jens Bülow,Jens F Rehfeld

doi:10.14814/phy2.14519

Abstract

Human studies have demonstrated that physiologically relevant changes in circulating glucagon‐like peptide‐1 (GLP‐1) elicit a rapid increase in renal sodium excretion when combined with expansion of the extracellular fluid volume. Other studies support the involvement of various gastrointestinal hormones, e.g., gastrin and cholecystokinin (CCK) in a gut‐kidney axis, responsible for a rapid‐acting feed‐forward natriuretic mechanism. This study was designed to investigate the hypothesis that the postprandial GLP‐1 plasma concentration is sensitive to the sodium content in the meal. Under fixed sodium intake for 4 days prior to each experimental day, 10 lean healthy male participants were examined twice in random order after a 12‐hr fasting period. Arterial blood samples were collected at 10–20‐min intervals for 140 min after 75 grams of oral glucose + 6 grams of oral sodium chloride (NaCl) load versus 75 grams of glucose alone. Twenty‐four‐hour baseline urinary sodium excretions were similar between study days. Arterial GLP‐1 levels increased during both oral glucose loads and were significantly higher at the 40–80 min period during glucose + NaCl compared to glucose alone. The postprandial arterial responses of CCK, gastrin, and glucose‐dependent insulinotropic polypeptide as well as glucose, insulin, and C‐peptide did not differ between the two study days. Arterial renin, aldosterone, and natriuretic peptides levels did not change within subjects or between study days. Angiotensin II levels were significantly lower at the time GLP‐1 was higher (60–80 min) during glucose + NaCl. Sodium intake in addition to a glucose load selectively amplifies the postprandial GLP‐1 plasma concentration. Thus, GLP‐1 may be part of an acute feed‐forward mechanism for natriuresis.

Highlights

Hypertension is one of the most common and important health problems worldwide because of its high frequency and concomitant risks of cardiovascular and kidney disease (Kearney et al, 2005; Mills et al, 2016)
Because glucagon-like peptide-1 (GLP-1) release is physiologically regulated by luminal stimuli in the small intestine, and since salt intake varies strongly within and between individuals, a direct salt sensitivity of L-cell GLP-1 release could provide a sequential, feed-forward signal that adds to the gastric/ duodenal signals from gastrin/CCK for renal sodium excretion
In this study we aimed to investigate whether postprandial GLP-1 secretion compared with the secretion of other nutrient-sensitive GI hormones is sensitive to an increased NaCl intake

Summary

Introduction

Hypertension is one of the most common and important health problems worldwide because of its high frequency and concomitant risks of cardiovascular and kidney disease (Kearney et al, 2005; Mills et al, 2016). There is increasing evidence of the importance of the GI tract in blood pressure regulation potentially through feed-forward effects on renal sodium handling. Whether the L-cell has sensors for sodium coupled to release of GLP-1 is not clarified This randomized, controlled cross-over study was designed to investigate the hypothesis that postprandial GLP-1 plasma concentrations are sensitive to an increased NaCl intake, supporting a feed-forward natriuretic system

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Conclusion