Reviews in Endocrine and Metabolic Disorders

, Volume 15, Issue 3, pp 197–207

Effects of GLP-1 in the Kidney

Article

DOI: 10.1007/s11154-014-9287-7

Cite this article as:
Skov, J. Rev Endocr Metab Disord (2014) 15: 197. doi:10.1007/s11154-014-9287-7

Abstract

The incretin hormone, glucagon-like peptide-1 (GLP-1), stimulates insulin secretion and forms the basis of a new drug class for diabetes treatment. GLP-1 has several extra-pancreatic properties which include effects on kidney function. Although renal GLP-1 receptors have been identified, their exact localization and physiological role are incompletely understood. GLP-1 increases natriuresis through inhibition of the sodium-hydrogen ion exchanger isoform 3 in the proximal tubule. This may in part explain why GLP-1 receptor agonists have antihypertensive effects. Glomerular filtration rate is regulated by GLP-1, but the mechanisms are complex and may depend on e.g. glycaemic conditions. Atrial natriuretic peptide or the renin-angiotensin system may be involved in the signalling of GLP-1-mediated renal actions. Several studies in rodents have shown that GLP-1 therapy is renoprotective beyond metabolic improvements in models of diabetic nephropathy and acute kidney injury. Inhibition of renal inflammation and oxidative stress probably mediate this protection. Clinical studies supporting GLP-1-mediated renal protection exist, but they are few and with limitations. However, acute and chronic kidney diseases are major global health concerns and measures improving renal outcome are highly needed. Therefore, the renoprotective potential of GLP-1 therapy need to be thoroughly investigated in humans.

Keywords

Glucagon-like peptide-1RenalGlomerular filtration rateNatriuresisDiabetic nephropathyAcute kidney injury

Abbreviations

ANG2

angiotensin II

AKI

acute kidney injury

ANP

atrial natriuretic peptide

ARB

angiotensin II receptor blocker

CrCl

creatinine clearance

DN

diabetic nephropathy

DPP-4

dipeptidyl peptidase IV

EMA

European Medicine Agency

ESRD

end-stage renal disease

GLP-1

glucagon-like peptide-1

GLP-1R

glucagon-like peptide-1 receptor

GFR

glomerular filtration rate

mRNA

messenger ribonucleic acid

NHE3

Na+/H+ exchanger isoform 3

PKA

protein kinase A

RAS

renin-angiotensin system

RBF

renal blood flow

ROS

reactive oxygen species

SGLT2

sodium-glucose linked transporter 2

STZ

streptozotocin

T2DM

type 2 diabetes mellitus

TGF

tubuloglomerular feedback

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Endocrinology and Internal MedicineAarhus University HospitalAarhusDenmark
  2. 2.Novo Nordisk A/SBagsvaerdDenmark