TY - JOUR
T1 - GLP-1 and the kidney
T2 - From physiology to pharmacology and outcomes in diabetes
AU - Muskiet, Marcel H.A.
AU - Tonneijck, Lennart
AU - Smits, Mark M.
AU - Van Baar, Michaël J.B.
AU - Kramer, Mark H.H.
AU - Hoorn, Ewout J.
AU - Joles, Jaap A.
AU - Van Raalte, Daniël H.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - The gastrointestinal tract-the largest endocrine network in human physiology-orchestrates signals from the external environment to maintain neural and hormonal control of homeostasis. Advances in understanding entero-endocrine cell biology in health and disease have important translational relevance. The gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) is secreted upon meal ingestion and controls glucose metabolism by modulating pancreatic islet cell function, food intake and gastrointestinal motility, amongst other effects. The observation that the insulinotropic actions of GLP-1 are reduced in type 2 diabetes mellitus (T2DM) led to the development of incretin-based therapies-GLP-1 receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors-for the treatment of hyperglycaemia in these patients. Considerable interest exists in identifying effects of these drugs beyond glucose-lowering, possibly resulting in improved macrovascular and microvascular outcomes, including in diabetic kidney disease. As GLP-1 has been implicated as a mediator in the putative gut-renal axis (a rapid-acting feed-forward loop that regulates postprandial fluid and electrolyte homeostasis), direct actions on the kidney have been proposed. Here, we review the role of GLP-1 and the actions of associated therapies on glucose metabolism, the gut-renal axis, classical renal risk factors, and renal end points in randomized controlled trials of GLP-1 receptor agonists and DPP-4 inhibitors in patients with T2DM.
AB - The gastrointestinal tract-the largest endocrine network in human physiology-orchestrates signals from the external environment to maintain neural and hormonal control of homeostasis. Advances in understanding entero-endocrine cell biology in health and disease have important translational relevance. The gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) is secreted upon meal ingestion and controls glucose metabolism by modulating pancreatic islet cell function, food intake and gastrointestinal motility, amongst other effects. The observation that the insulinotropic actions of GLP-1 are reduced in type 2 diabetes mellitus (T2DM) led to the development of incretin-based therapies-GLP-1 receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors-for the treatment of hyperglycaemia in these patients. Considerable interest exists in identifying effects of these drugs beyond glucose-lowering, possibly resulting in improved macrovascular and microvascular outcomes, including in diabetic kidney disease. As GLP-1 has been implicated as a mediator in the putative gut-renal axis (a rapid-acting feed-forward loop that regulates postprandial fluid and electrolyte homeostasis), direct actions on the kidney have been proposed. Here, we review the role of GLP-1 and the actions of associated therapies on glucose metabolism, the gut-renal axis, classical renal risk factors, and renal end points in randomized controlled trials of GLP-1 receptor agonists and DPP-4 inhibitors in patients with T2DM.
UR - http://www.scopus.com/inward/record.url?scp=85030447466&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/nrneph.2017.123
DO - https://doi.org/10.1038/nrneph.2017.123
M3 - Review article
C2 - 28869249
SN - 1759-5061
VL - 13
SP - 605
EP - 628
JO - Nature Reviews Nephrology
JF - Nature Reviews Nephrology
IS - 10
ER -