glucagon-like-peptide-1-(7-36)amide and Kidney-Failure--Chronic

The affect of the kidneys in elimination and degradation of intact incretin hormones and their truncated metabolites is unclear.. 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.. 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.. 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).. 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.

Topics: Adult; Blood Glucose; Denmark; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Fasting; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Humans; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Peptide Fragments; Proteolysis; Pyrazines; Renal Dialysis; Sitagliptin Phosphate; Triazoles