TY - JOUR
AU1 - Deacon, C F
AU2 - Nauck, M A
AU3 - Toft-Nielsen, M
AU4 - Pridal, L
AU5 - Willms, B
AU6 - Holst, J J
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 rapidly degraded 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.
TI - 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.
JF - Diabetes
DO - 10.2337/diab.44.9.1126
DA - 1995-10-04
UR - https://www.deepdyve.com/lp/pubmed/both-subcutaneously-and-intravenously-administered-glucagon-like-IENouOqhi1
SP - 1126
EP - 31
VL - 44
IS - 9
DP - DeepDyve
ER -