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Abstract: TH-PO1209

The Gut-Kidney Axis in Man: GLP-1's Natriuretic Action Is Abolished by the GLP-1 Receptor Antagonist Exendin 9-39

Session Information

Category: Fluid and Electrolytes

Authors

  • Asmar, Ali, Rigshospitalet, Copenhagen, Denmark
  • Cramon, Per Karkov, Bispebjerg University Hospital, Copenhagen, Denmark
  • Asmar, Meena, Steno Diabetes Center, Odense, Denmark
  • Simonsen, Lene, Bispebjerg University Hospital, Copenhagen, Denmark
  • Sorensen, Charlotte Mehlin, University of Copenhagen, Copenhagen, Denmark
  • Madsbad, Sten, Hvidovre Hospital, Hvidovre, Denmark
  • Hovind, Peter, Bispebjerg University Hospital, Copenhagen, Denmark
  • Holst, Jens Juul, The Panum Institute, University of Copenhagen, Copenhagen N, Denmark
  • Jensen, Boye, University of Southern Denmark, Odense C, Denmark
  • Bülow, Jens, University of Copenhagen, Copenhagen, Denmark
Background

We have recently demonstrated that extracellular fluid volume expansion in healthy participants uncovered a natriuretic action of GLP-1 probably via a tubular mechanism secondary to suppression of angiotensin II (ANG II). In the current study, we designed an additional study day to investigate whether GLP-1’s natriuretic effect is mediated via activation and signaling of the GLP-1 receptor.

Methods

Under fixed sodium intake for 4 days before each study day, 6 healthy male participants were recruited from our recent study (1) and examined during a 3-hour infusion of GLP-1 (1.5 pmol/kg/min) together with a 3.5-hour infusion of the GLP-1 receptor antagonist, exendin 9-39 (Ex 9-39) (900 pmol/kg/min), initiated 30 minutes before start of GLP-1 infusion. Timed urine collections were conducted throughout the experiments. Renal plasma flow (RPF), glomerular filtration rate (GFR), and uptake and release of hormones and ions were measured via Fick's principle after catheterization of a renal vein.

Results

During co-infusion of GLP-1 and Ex 9-39, urinary sodium and osmolar excretions remained at baseline levels compared to a mean 2-fold natriuretic effect during GLP-1 infusion alone. Arterial plasma ANG II levels were unaffected during co-infusion of GLP-1 and Ex 9-39, whereas ANG II decreased significantly during GLP-1 alone. Arterial plasma renin levels decreased similarly on the two study days, and arterial aldosterone levels remained unchanged on both days. RPF and GFR remained unchanged on both days.

Conclusion

GLP-1’s natriuretic action is abolished by the GLP-1 receptor antagonist Ex 9-39, probably via the antagonized GLP-1-mediated ANG II suppression.

1Asmar A et al. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2509-2519.

Funding

  • Private Foundation Support