title: Acute renal haemodynamic effects of glucagon-like peptide-1 receptor agonist exenatide in healthy overweight men.
abstract: OBJECTIVE
  To determine the acute effect of glucagon-like peptide-1 (GLP-1) receptor agonist exenatide and the involvement of nitric oxide (NO) on renal haemodynamics and tubular function, in healthy overweight men.
  
  
  METHODS
  Renal haemodynamics and tubular electrolyte handling were measured in 10 healthy overweight men (aged 20-27 years; BMI 26-31 kg/m(2)) during intravenous administration of placebo (saline 0.9%), exenatide, and exenatide combined with the NO-synthase inhibitor L-N(G)-monomethyl arginine (L-NMMA). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippurate clearance techniques, respectively, based on timed urine sampling. Glomerular hydrostatic pressure and vascular resistance of afferent and efferent renal arterioles were calculated using the Gomez formulae. Urinary electrolytes, osmolality and pH were also measured.
  
  
  RESULTS
  GFR increased by a mean of 18 ± 20 (+20%; p = 0.021) and ERPF increased by a median (interquartile range) of 68 (26; 197) ml/min/1.73 m(2) (+14%; p = 0.015) during exenatide infusion versus placebo. During L-NMMA infusion, exenatide increased GFR by mean 8 ± 12 ml/min/1.73 m(2) (+9%; p = 0.049). Exenatide increased estimated glomerular pressure by +6% (p = 0.015) and reduced afferent renal vascular resistance by -33% (p = 0.038), whereas these effects were blunted during L-NMMA infusion. Exenatide increased absolute and fractional sodium excretion, urinary osmolality and urinary pH. The tubular effects of exenatide were not altered by concomitant L-NMMA infusion.
  
  
  CONCLUSIONS
  Exenatide infusion in healthy overweight men acutely increases GFR, ERPF and glomerular pressure, probably by reducing afferent renal vascular resistance, and at least partially in an NO-dependent manner. As baseline renal haemodynamics in patients with type 2 diabetes differ from those in healthy individuals, clinical studies on the renal effects of GLP-1 receptor agonists are warranted.
authors.affiliation: Diabetes Centre, Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: M H A
authors.initials: MH
authors.lastname: Muskiet
authors.affiliation: Diabetes Centre, Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Tonneijck
authors.affiliation: Diabetes Centre, Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: Smits
authors.affiliation: Diabetes Centre, Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: M H H
authors.initials: MH
authors.lastname: Kramer
authors.affiliation: Diabetes Centre, Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Diamant
authors.affiliation: Department of Nephrology and Hypertension, University Medical Centre, Utrecht, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Joles
authors.affiliation: Diabetes Centre, Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: D H
authors.initials: DH
authors.lastname: van Raalte
mesh_terms: D000328:Adult; D015992:Body Mass Index; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000077270:Exenatide; D005919:Glomerular Filtration Rate / Q000187:drug effects; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007684:Kidney Tubules / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050177:Overweight / Q000378:metabolism / Q000503:physiopathology* / Q000652:urine; D010455:Peptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects*; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D004791:Enzyme Inhibitors; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D019323:omega-N-Methylarginine; D000077270:Exenatide; D019001:Nitric Oxide Synthase; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: GLP‐1 receptor agonist; L‐NMMA; exenatide; nitric oxide; renal haemodynamics