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Glucagon‐Like Peptide (GLP1) Agonist Increases GFR and Suppresses Proximal Reabsorption
Author(s) -
Thomson Scott Culver,
Kashkouli Ali,
Singh Prabhleen
Publication year - 2010
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.24.1_supplement.1059.32
Subject(s) - exenatide , medicine , endocrinology , agonist , reabsorption , tubuloglomerular feedback , chemistry , kidney , lixisenatide , renal function , nephron , tubular fluid , loop of henle , type 2 diabetes , receptor , diabetes mellitus
The incretin, GLP1, is released by the gut in response to fat or CHO and lowers glucose by effects on the stomach and pancreas. GLP1 receptors are also in kidney. We examined the effects of a GLP1 agonist, exenatide, on glomerular and tubular function in normal and diabetic rats. GFR (inulin clearance) and urine flow rate were measured in awake rats following exenatide (1 nmol sq) or placebo (n=5 each). Micropuncture was done in normal and hyperfiltering STZ‐diabetic rats before and during exenatide (1 nmol/h iv). Single nephron (SN) GFR and proximal reabsorption (Jprox) were measured at both extremes of tubuloglomerular feedback (TGF) activation (loop of Henle perfusion). ANCOVA with SNGFR as covariate tested for primary effects on Jprox. Conscious rats on exenatide had higher GFR (4.3±0.2 vs 2.2±0.3 ml/min, p=0.001) and urine flow (34±4 vs 12±3 ul/min, p=0.002). Micropuncture results are shown in the table‐*P<0.05 for exenatide. Total 114 tubular fluid collections from 6 rats.SNGFR no TGF (nl/min) SNGFR max TGF Jprox adjusted for SNGFRControl 40±5 29±7 26±1 + Exenatide 70±4* 50±6* 18±1* Diabetes 52±5 33±6 26±1 + Exenatide 65±4* 53±6* 16±1*Exenatide increases GFR and is a potent proximal diuretic, implying effects on both glomerulus and tubule. It is a mystery why the GLP1 receptor, whose natural agonist responds to fat ingestion, should have such capacities to raise GFR and suppress proximal reabsorption.