GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes
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.
|Persistent URL||dx.doi.org/10.1038/nrneph.2017.123, hdl.handle.net/1765/102250|
|Journal||Nature Reviews Nephrology|
Muskiet, M.H.A, Tonneijck, L, Smits, M.M, van Baar, M.J.B. (Michaël J B), Kramer, M.H.H, Hoorn, E.J, … van Raalte, D.H. (2017). GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes. Nature Reviews Nephrology (Vol. 13, pp. 605–628). doi:10.1038/nrneph.2017.123