title: The elimination rates of intact GIP as well as its primary metabolite, GIP 3-42, are similar in type 2 diabetic patients and healthy subjects.
abstract: The incretin hormone, glucose-dependent insulinotropic polypeptide (GIP, previously known as gastric inhibitory polypeptide), is rapidly degraded to the biologically inactive metabolite GIP (3-42) in the circulation, but little is known about the kinetics of the intact hormone and the metabolite and whether differences exist between patients with type 2 diabetes mellitus and healthy subjects. We examined eight type 2 diabetic patients (six men, two women); mean (range) age: 59 (48-69) years; BMI: 31.6 (26.0-37.7) kg/m2; HbA1C: 9.0 (8.2-13.2) %; fasting plasma glucose (FPG): 10.0 (8.3-13.2) mmol/l and 8 healthy subjects matched for age, gender and BMI. An intravenous bolus injection of GIP (7.5 nmol) was given and venous blood samples were drawn the following 45 minutes. Peak concentrations of total GIP (intact+metabolite, mean+/-SEM) and intact GIP (in brackets) were 920+/-91 (442+/-52) pmol/l in the type 2 diabetic patients and 775+/-68 (424+/-30) pmol/l in the healthy subjects (NS). GIP was eliminated rapidly with the clearance rate for intact GIP being 2.3+/-0.2 l/min in the type 2 diabetic patients and 2.4+/-0.2 l/min in the healthy subjects (NS). The volumes of distributions were similar in the two groups and ranged from 8 to 21 l per subject. The primary metabolite, GIP 3-42, generated through the action of dipeptidyl peptidase IV (DPP-IV), was eliminated with a mean half-life of 17.5 and 20.5 min in patients and healthy subjects (NS).
  
  
  CONCLUSIONS
  Elimination of GIP is similar in obese type 2 diabetic patients and matched healthy subjects. Differences in elimination of GIP and its primary metabolite, therefore, do not seem to contribute to the defective insulinotropic effect of GIP in type 2 diabetes.
authors.affiliation: Department of Internal Medicine F, Gentofte Hospital, Denmark. t.vilsboll@dadlnet.dk
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.forename: Henrik
authors.initials: H
authors.lastname: Agersø
authors.forename: Torsten
authors.initials: T
authors.lastname: Lauritsen
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Deacon
authors.forename: Kasper
authors.initials: K
authors.lastname: Aaboe
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.forename: Thure
authors.initials: T
authors.lastname: Krarup
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; C515715:gastric inhibitory polypeptide (3-42); D005749:Gastric Inhibitory Polypeptide