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

The elimination rates of intact GIP as well as its primary metabolite, GIP 3-42, are similar in... 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/m 2 ; HbA 1C : 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). Conclusion: 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Regulatory Peptides Elsevier

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

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Publisher
Elsevier
Copyright
Copyright © 2006 Elsevier B.V.
ISSN
0167-0115
eISSN
1873-1686
D.O.I.
10.1016/j.regpep.2006.07.007
Publisher site
See Article on Publisher Site

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/m 2 ; HbA 1C : 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). Conclusion: 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.

Journal

Regulatory PeptidesElsevier

Published: Dec 10, 2006

References

  • Incretins, insulin secretion and type 2 diabetes mellitus
    Vilsboll, T.; Holst, J.J.
  • Glucagon-like peptide 1 undergoes differential tissue-specific metabolism in the anesthetized pig
    Deacon, C.F.; Pridal, L.; Klarskov, L.; Olesen, M.; Holst, J.J.
  • What do we know about the secretion and degradation of incretin hormones?
    Deacon, C.F.
  • Reduced incretin effect in type 2 (non-insulin-dependent) diabetes
    Nauck, M.; Stockmann, F.; Ebert, R.; Creutzfeldt, W.
  • Incretin concept today
    Creutzfeldt, W.
  • Endoproteolysis of glucagon-like peptide (GLP)-1(7-36) amide by ectopeptidases in RINm5F cells
    HupeSodmann, K.; Goke, R.; Goke, B.; Thole, H.H.; Zimmermann, B.; Voigt, K.

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