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Original Articles

Both Subcutaneously and Intravenously Administered Glucagon-Like Peptide I Are Rapidly Degraded From the NH2-Terminus in Type II Diabetic Patients and in Healthy Subjects

  1. Carolyn F Deacon,
  2. Michael A Nauck,
  3. Maibritt Toft-Nielsen,
  4. Lone Pridal,
  5. Berend Willms and
  6. Jens J Holst
  1. Department of Medical Physiology, Panum Institute, University of Copenhagen Copenhagen
  2. Department of Endocrinology, Hvidovre Hospital Copenhagen
  3. Department of Diabetes Pharmacology, Novo Nordisk A/S Bagsvaerd, Denmark
  4. Department of Medicine, Ruhr University Bochum
  5. Fachklinik für Diabetes und Stoffwech-selkrankheiten, Bad Lauterberg Germany
  1. Address correspondence and reprint requests to Dr. C.F. Deacon, Department of Medical Physiology, Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
Diabetes 1995 Sep; 44(9): 1126-1131. https://doi.org/10.2337/diab.44.9.1126
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Abstract

To fate of exogenous glucagon-like peptide I (GLP-I)(7–36) amide was studied in nondiabetic and type II diabetic subjects using a combination of high-pressure liquid chromatography (HPLC), specific radioimmunoassays (RIAs), and a sensitive enzyme-linked immunosorbent assay (ELISA), whereby intact biologically active GLP-I and its metabolites could be determined. After GLP-I administration, the intact peptide could be measured using an NH2-terminally directed RIA or ELISA,while the difference in concentration between these assays and a COOH-terminal–specific RIA allowed determination of NH2-terminally truncated metabolites. Subcutaneous GLP-I was rapidlydegraded in a time-dependent manner, forming a metabolite, which co-eluted on HPLC with GLP-I(9–36) amide and had the same immunoreactive profile. Thirty minutes after subcutaneous GLP-I administration to diabetic patients (n = 8), the metabolite accounted for 88.5 ± 1.9% of the increase in plasma immunoreactivity determined by the COOH-terminal RIA, which was higher than the levels measured in healthy subjects (78.4 ± 3.2%; n = 8; P < 0.05). Intravenously infused GLP-I was also extensively degraded, but no significant differences were seen between the two groups. Intact GLP-I accounted for only 19.9 ± 3.4% of the increase in immunoreactivity measured with the COOH-terminal RIA in normal subjects (n = 8), and 25.0 ± 4.8% of the increase in diabetic subjects (n = 8), the remainder being the NH2-terminally truncated metabolite.

  • Received March 7, 1995.
  • Revision received May 18, 1995.
  • Accepted May 18, 1995.
  • Copyright © 1995 by the American Diabetes Association

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September 1995, 44(9)
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Both Subcutaneously and Intravenously Administered Glucagon-Like Peptide I Are Rapidly Degraded From the NH2-Terminus in Type II Diabetic Patients and in Healthy Subjects
Carolyn F Deacon, Michael A Nauck, Maibritt Toft-Nielsen, Lone Pridal, Berend Willms, Jens J Holst
Diabetes Sep 1995, 44 (9) 1126-1131; DOI: 10.2337/diab.44.9.1126

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Both Subcutaneously and Intravenously Administered Glucagon-Like Peptide I Are Rapidly Degraded From the NH2-Terminus in Type II Diabetic Patients and in Healthy Subjects
Carolyn F Deacon, Michael A Nauck, Maibritt Toft-Nielsen, Lone Pridal, Berend Willms, Jens J Holst
Diabetes Sep 1995, 44 (9) 1126-1131; DOI: 10.2337/diab.44.9.1126
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