PT - JOURNAL ARTICLE AU - Deacon, Carolyn F AU - Nauck, Michael A AU - Toft-Nielsen, Maibritt AU - Pridal, Lone AU - Willms, Berend AU - Holst, Jens J TI - Both Subcutaneously and Intravenously Administered Glucagon-Like Peptide I Are Rapidly Degraded From the NH<sub>2</sub>-Terminus in Type II Diabetic Patients and in Healthy Subjects AID - 10.2337/diab.44.9.1126 DP - 1995 Sep 01 TA - Diabetes PG - 1126--1131 VI - 44 IP - 9 4099 - http://diabetes.diabetesjournals.org/content/44/9/1126.short 4100 - http://diabetes.diabetesjournals.org/content/44/9/1126.full SO - Diabetes1995 Sep 01; 44 AB - 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 &lt; 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.