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/diabetes.44.9.1126
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发表时间：
1995-09-01
期刊：
影响因子：
7.7
通讯作者：
HOLST, JJ
中科院分区：
文献类型：
--
作者：
DEACON, CF;NAUCK, MA;HOLST, JJ
采用高压液相色谱法（HPLC）、特异性放射免疫测定法（RIA）和灵敏的酶联免疫吸附测定法（ELISA），在非糖尿病和II型糖尿病受试者中研究了外源性胰高血糖素样肽I（GLP-I）（7-36）酰胺的命运，从而可以测定完整的生物活性GLP-I及其代谢产物。GLP-1给药后，可以使用NH 2-末端定向RIA或ELISA测量完整肽，而这些测定和COOH-末端特异性RIA之间的浓度差异允许测定NH末端截短代谢物。皮下注射GLP-I以时间依赖性方式快速降解，形成代谢产物，在HPLC上与GLP-I（9-36）酰胺共洗脱，具有相同的免疫反应性特征。糖尿病患者（n = 8）皮下注射GLP-1 30分钟后，代谢产物占COOH末端RIA测定的血浆免疫反应性增加的88.5 +/- 1.9%，高于健康受试者中测定的水平（78.4 +/- 3.2%; a = 8; P < 0.05）。腹腔内输注的GLP-I也被广泛降解，但两组之间未见显著差异。在正常受试者（n = 8）中，完整GLP-1仅占COOH末端RIA测定的免疫反应性增加的19.9 +/- 3.4%，在糖尿病受试者（n = 8）中占25.0 +/- 4.8%，其余为NH 2末端截短代谢产物。
The 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 NH,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%; a = 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.