title: Diuretic and Natriuretic Effects of Dipeptidyl Peptidase-4 Inhibitor Teneligliptin: The Contribution of Glucagon-like Peptide-1.
abstract: Glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are antidiabetic agents; however, their mechanisms of action are different. GLP-1R and DPP-4 are also expressed in the renal proximal tubular brush border, where they regulate Na reabsorption. We investigated whether the DPP-4 inhibitor, teneligliptin, has diuretic and natriuretic effects and whether these are associated with the stimulation of the GLP-1R in rats. Oral administration of teneligliptin resulted in a reduction of plasma DPP-4 activity over 6 hours, as well as an induction of diuresis and natriuresis. Although teneligliptin did not change the increase in blood glucose levels by glucose loading, percentage of urine volume and Na/K ratio with teneligliptin to vehicle were augmented by glucose loading. Peak levels of plasma GLP-1 did not change after oral administration of teneligliptin when glucose was not loaded but increased at least 2-fold with glucose loading. Furthermore, the natriuretic effect of teneligliptin was inhibited by the GLP-1R antagonist, exendin9-39, whereas the diuresis was not affected. These results suggest that the mechanism of natriuresis was different from that of diuresis, and the natriuresis is associated with the stimulation of GLP-1R. There may be mechanistic differences in DPP-4 inhibition between diuresis and natriuresis.
authors: *Division of Cardiovascular Medicine, Toho University Ohashi Medical Center, Tokyo, Japan; and †Laboratory for Metabolic Homeostasis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
authors: Masao
authors: M
authors: Moroi
authors: Tetsuya
authors: T
authors: Kubota
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D008297:Male; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D045283:Natriuretic Agents / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D053778:Thiazolidines / Q000494:pharmacology*
chemical_list: C579035:3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004232:Diuretics; D045283:Natriuretic Agents; D011720:Pyrazoles; D053778:Thiazolidines; D052216:Glucagon-Like Peptide 1