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

Abstract

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.

• Authors: Marcel H A Muskiet, Lennart Tonneijck, Mark M Smits, Michaël J B van Baar, Mark H H Kramer, Ewout J Hoorn, Jaap A Joles, Daniël H van Raalte
• Journal: Nature reviews. Nephrology (Nat Rev Nephrol) Vol. 13 Issue 10 Pg. 605-628 (Oct 2017) ISSN: 1759-507X [Electronic] England
• PMID: 28869249 (Publication Type: Journal Article, Review)

Chemical References

• Blood Glucose
• Dipeptidyl-Peptidase IV Inhibitors
• Hypoglycemic Agents
• Incretins
• Glucagon-Like Peptide 1

Topics

• Blood Glucose (drug effects, metabolism)
• Diabetes Mellitus, Type 2 (drug therapy, metabolism, physiopathology)
• Diabetic Nephropathies (drug therapy, metabolism, physiopathology)
• Dipeptidyl-Peptidase IV Inhibitors (pharmacology)
• Glucagon-Like Peptide 1 (physiology)
• Humans
• Hyperglycemia (drug therapy, metabolism, physiopathology)
• Hypoglycemic Agents (pharmacology)
• Incretins (pharmacology)
• Risk Factors