Premium
GLP1 receptor activation and DPP‐4 inhibition increase GFR and induce natriuresis and diuresis in mice
Author(s) -
Rieg Timo,
Gerasimova Maria,
Drucker Daniel J,
Vallon Volker
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.666.4
Subject(s) - natriuresis , diuresis , chemistry , endocrinology , medicine , pharmacology , kidney
Dipeptidyl peptidase‐4 (DPP‐4) degrades glucagon‐like peptide‐1 (GLP1), which stimulates glucose‐dependent insulin release. DPP‐4 inhibitors (like alogliptin; AGT) and GLP1 receptor (GLP1R) agonists (like exendin‐4, EX4) are novel antidiabetic drugs. The DPP‐4/GLP1‐R system is also expressed in proximal tubular brush border and may regulate Na+ reabsorption. Here we performed two‐period inulin clearance studies in anesthetized non‐diabetic wild‐type (WT) mice and mice lacking the GLP1R (−/−). First, EX4 (10μg/kg i.v.) increased urinary fluid and Na+ excretion in WT mice but not in Glp1r−/− mice (by 76±25 vs −6±5% and 140±45 vs −9±12%; n=11–12; P<0.001 each). This was associated with an increase in GFR and fractional Na+ excretion in WT vs. Glp1r−/− (by 16±9 vs −10±3%, 118±45 vs 3±15%, P<0.05 each). Second, application of AGT (10mg/kg i.v.) increased GFR and absolute and fractional urinary excretion of fluid and Na+ in WT mice compared with vehicle control (by 11±3 vs −12±6%, 57±16 vs −12±4%, 42±17 vs 0±5%, 63±23 vs −29±11%, 45±22 vs −18±7%, all P<0.05). Neither AGT nor EX4 altered blood pressure. The results show that direct activation of the GLP1R or inhibition of DPP4 increase GFR as well as urinary fluid and sodium excretion. The effect on GFR is consistent with a renal vasodilatory influence of the GLP1‐R. The observed effect on fractional Na+ excretion may reflect an additional direct tubular effect.