title: The potential for renoprotection with incretin-based drugs.
abstract: Incretin-based drugs, i.e., glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are widely used for the treatment of type 2 diabetes. In addition to the primary role of incretins in stimulating insulin secretion from pancreatic β-cells, they have extra pancreatic functions beyond glycemic control. Indeed, recent studies highlight the potential beneficial effects of incretin-based therapy in diabetic kidney disease (DKD). Experimental studies using various diabetic models suggest that incretins protect the vascular endothelium from injury by binding to GLP-1 receptors, thereby ameliorating oxidative stress and the local inflammatory response, which reduces albuminuria and inhibits glomerular sclerosis. In addition, there is some evidence that GLP-1 receptor agonists and DPP-4 inhibitors mediate sodium excretion and diuresis to lower blood pressure. The pleiotropic actions of DPP-4 inhibitors are ascribed primarily to their effects on GLP-1 signaling, but other substrates of DPP-4, such as brain natriuretic peptide and stromal-derived factor-1α, may have roles. In this review, we summarize recent studies of the roles of incretin-based therapy in ameliorating DKD and its complications.
authors.affiliation: Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Higashijima
authors.affiliation: Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Wada
authors.affiliation: Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nangaku
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D054795:Incretins / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D018027:Receptors, Glucagon / Q000819:agonists*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy; D015398:Signal Transduction
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1