Review,
The GLP-1-mediated gut-kidney cross talk in humans: mechanistic insight
Affiliations
- [1] Odense Univ Hosp, Dept Nephrol, Odense, Denmark [NORA names: Region of Southern Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD];
- [2] Odense Univ Hosp, Dept Nephrol, Odense, Denmark [NORA names: SDU University of Southern Denmark; University; Denmark; Europe, EU; Nordic; OECD];
- [3] Copenhagen Univ Hosp, Bispebjerg & Frederiksberg Hosp, Dept Clin Physiol & Nucl Med, Copenhagen, Denmark [NORA names: Capital Region of Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD];
- [4] Copenhagen Univ Hosp Rigshosp, Dept Clin Physiol & Nucl Med, Copenhagen, Denmark [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
- [5] Copenhagen Univ Hosp Rigshosp, Dept Clin Physiol & Nucl Med, Copenhagen, Denmark [NORA names: Capital Region of Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD]
Abstract
Incretin-based therapy is an antidiabetic and antiobesity approach mimicking glucagon-like peptide-1 (GLP-1) with additional end-organ protection. This review solely focuses on randomized, controlled mechanistic human studies, investigating the renal effects of GLP-1. There is no consensus about the localization of GLP-1 receptors (GLP-1Rs) in human kidneys. Rodent and primate data suggest GLP-1R distribution in smooth muscle cells in the preglomerular vasculature. Native GLP-1 and GLP-1R agonists elicit renal effects. Independently of renal plasma flow and glomerular filtration rate, GLP-1 has a natriuretic effect but only during volume expansion. This is associated with high renal extraction of GLP-1, suppression of angiotensin II, and increased medullary as well as cortical perfusion. These observations may potentially indicate that impaired GLP-1 sensing could establish a connection between salt sensitivity and insulin resistance. It is concluded that a functional GLP-1 kidney axis exists in humans, which may play a role in renoprotection.