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GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes

Nat Rev Nephrol. 2017 Oct;13(10):605-628. doi: 10.1038/nrneph.2017.123. Epub 2017 Sep 4.GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes.Muskiet MHA1, Tonneijck L1, Smits MM1, van Baar MJB1, Kramer MHH1, Hoorn EJ2, Joles JA3, van Raalte DH1.Author information1Diabetes Center, Department of Internal Medicine, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands.2Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus Medical Center, s-Gravendijkwal 230, 3015 CE, Rotterdam, Netherlands.3Department of Nephrology and Hypertension, University Medical Centre, Heidelberglaan 100, 3584 CX, Utrecht, Netherlands.AbstractThe 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.PMID: 28869249 DOI: 10.1038/nrneph.2017.123 [Indexed for MEDLINE] SharePublication type, MeSH terms, SubstancesPublication typeReviewMeSH termsBlood Glucose/drug effectsBlood Glucose/metabolismDiabetes Mellitus, Type 2/drug therapy*Diabetes Mellitus, Type 2/metabolism*Diabetes Mellitus, Type 2/physiopathologyDiabetic Nephropathies/drug therapy*Diabetic Nephropathies/metabolism*Diabetic Nephropathies/physiopathologyDipeptidyl-Peptidase IV Inhibitors/pharmacology*Glucagon-Like Peptide 1/physiology*HumansHyperglycemia/drug therapy*Hyperglycemia/metabolism*Hyperglycemia/physiopathologyHypoglycemic Agents/pharmacology*Incretins/pharmacology*Risk FactorsSubstancesBlood GlucoseDipeptidyl-Peptidase IV InhibitorsHypoglycemic AgentsIncretinsGlucagon-Like Peptide 1LinkOut - more resourcesFull Text SourcesNature Publishing GroupOvid Technologies, Inc.Other Literature SourcesSee the articles recommended by F1000Prime's Faculty of more than 8,000 leading experts in Biology and Medicine. - Faculty of 1000MedicalClinicalTrials.govDiabetes - Genetic AllianceHyperglycemia - MedlinePlus Health InformationDiabetic Kidney Problems - MedlinePlus Health InformationDiabetes Medicines - MedlinePlus Health InformationDiabetes Type 2 - MedlinePlus Health Information

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