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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 …