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Effects of GLP-1 in the Kidney

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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.

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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

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Conflict of interest

J.S. has a PhD fellowship in a joint collaboration between Aarhus University Hospital and Novo Nordisk.

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  1. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Norrebrogade 44, 8000, Aarhus, Denmark

    Jeppe Skov

  2. Novo Nordisk A/S, 2880, Bagsvaerd, Denmark

    Jeppe Skov

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Skov, J. Effects of GLP-1 in the Kidney. Rev Endocr Metab Disord 15, 197–207 (2014). https://doi.org/10.1007/s11154-014-9287-7

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