The GLP-1-mediated Gut-Kidney Cross Talk in Humans: Mechanistic Insight

Abstract

Incretin-based therapy is an anti-diabetic and anti-obesity approach mimicking glucagon-like peptide 1 (GLP-1) with additional end-organ protection. This review solely focuses on randomized, controlled mechanistic human studies on renal effect of GLP-1. There is not consensus about the localization of GLP-1 receptors (GLP-1R) 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 (GFR), 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 (ANG 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 human which may play a role in renoprotection.