Elimination and degradation of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with end-stage renal disease.
BACKGROUND
The affect of the kidneys in elimination and degradation of intact incretin hormones and their truncated metabolites is unclear.


OBJECTIVE
To evaluate elimination and degradation of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in patients with dialysis-dependent kidney failure.


METHODS
Twelve non-diabetic patients treated with chronic hemodialysis and 12 control subjects were examined in a double-blind, randomized, matched observational study at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Over 4 separate study days, synthetic human GIP or GLP-1 was infused with or without concurrent inhibition of dipeptidyl peptidase 4 using sitagliptin or placebo. Plasma concentrations of glucose, insulin, glucagon, and intact and total forms of GLP-1 or GIP were measured repeatedly. Plasma half-life (T1/2), metabolic clearance rate (MCR), area under curve, and volume of distribution for intact and metabolite levels of GLP-1 and GIP were calculated.


RESULTS
Fasting concentrations of intact GLP-1 and GIP were increased in dialysis patients (P < .001) whereas fasting levels of GLP-1 and GIP metabolites did not differ between groups (P > .738). MCRs of intact GLP-1 and GIP, and the GLP-1 metabolite were reduced in dialysis patients on the placebo day (P < .009), and T1/2 of intact and metabolite forms of GLP-1 and GIP were comparable between groups (P > .121).


CONCLUSIONS
Unexpectedly, degradation and elimination of the intact and metabolite forms of GLP-1 and GIP seemed preserved, although reduced, in patients with dialysis-dependent kidney failure.
Department of Nephrology (T.I., M.B.J., M.H., B.F.-R.), Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark; Diabetes Research Division, Department of Internal Medicine (F.K.K., M.C.), Gentofte Hospital, University of Copenhagen, DK-2900 Hellerup, Denmark; and The NNF Center for Basic Metabolic Research, Department of Biomedical Sciences (F.K.K., J.J.H.), the Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Thomas
T
Idorn
Filip K
FK
Knop
Morten B
MB
Jørgensen
Mikkel
M
Christensen
Jens J
JJ
Holst
Mads
M
Hornum
Bo
B
Feldt-Rasmussen
D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D001786:Blood Glucose / Q000378:metabolism; D003718:Denmark; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage; D005215:Fasting / Q000097:blood / Q000652:urine; D005749:Gastric Inhibitory Polypeptide / Q000008:administration & dosage / Q000493:pharmacokinetics; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000493:pharmacokinetics; D007328:Insulin / Q000097:blood; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics; D059748:Proteolysis; D011719:Pyrazines / Q000008:administration & dosage; D006435:Renal Dialysis / Q000009:adverse effects; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000008:administration & dosage
D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005749:Gastric Inhibitory Polypeptide; C101760:gastric inhibitory polypeptide (1-42); D052216:Glucagon-Like Peptide 1; C055453:glucagon-like peptide 1 (7-36)amide; D007328:Insulin; D010446:Peptide Fragments; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles