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
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
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DOI：
10.2337/diab.44.9.1126
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发表时间：
1995-09
期刊：
影响因子：
7.7
通讯作者：
C. Deacon;M. Nauck;M. Toft-Nielsen;L. Pridal;B. Willms;J. Holst
中科院分区：
文献类型：
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作者：
C. Deacon;M. Nauck;M. Toft-Nielsen;L. Pridal;B. Willms;J. Holst
采用高压液相色谱（HPLC）、特异性放射免疫测定（RIAs）和灵敏酶联免疫吸附测定（ELISA）相结合的方法，研究了非糖尿病和II型糖尿病受试者中外源性胰高血糖素样肽I (GLP-I)（7-36）酰胺的宿命，由此可以确定完整的生物活性GLP-I及其代谢产物。glp - 1给药后，可以使用nh2末端定向RIA或ELISA测量完整肽，而这些检测方法与cooh末端特异性RIA之间的浓度差异允许测定nh2末端截断的代谢物。皮下glp - 1以时间依赖性的方式快速降解，形成代谢物，在HPLC上与glp - 1（9-36）酰胺共洗脱，具有相同的免疫反应谱。糖尿病患者（n = 8）皮下给予GLP-I后30分钟，血浆免疫反应性升高（cooh末端RIA测定）中，GLP-I代谢物占88.5±1.9%，高于健康人（78.4±3.2%,n = 8, P < 0.05）。静脉注射glp - 1也被广泛降解，但两组之间没有明显差异。完整GLP-I仅占正常受试者（n = 8） cooh末端RIA测定的免疫反应性增加的19.9±3.4%，占糖尿病受试者（n = 8）的25.0±4.8%，其余为nh2末端截断代谢物。
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.