Orskov C, Jeppesen J, Madsbad S, Holst J J
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
J Clin Invest. 1991 Feb;87(2):415-23. doi: 10.1172/JCI115012.
We investigated the major products of proglucagon (PG) processing in plasma in the fasting state, after intravenous arginine and after an oral glucose load in noninsulin-dependent diabetics (NIDDM) and in weight matched controls using specific radioimmunoassays and analytical gel filtration. In the fasting state the glucagonlike peptide-1 (GLP-1) immunoreactivity was significantly elevated in the NIDDM group compared with the control group. Both after intravenous arginine and after an oral glucose load a rise in the plasma concentrations of all immunoreactive moieties measured was seen. All integrated incremental responses after intravenous arginine were identical in the two groups. After oral glucose the insulin concentrations in plasma were lower and the concentrations of all proglucagon products were higher in the NIDDM group compared to the control group. The gel filtration analysis showed that arginine stimulated the secretion of pancreatic glucagon (PG 33-61), major proglucagon fragment (PG 72-158) and probably GLP-1 (PG 72-107 amide) in both groups, whereas oral glucose stimulated the secretion of glicentin (PG 1-69) and intestinal GLP-1 (PG 78-107 amide), an insulinotropic hormone. The elevated levels of immunoreactive GLP-1 in diabetics in the fasting state were mainly due to an increased concentration of major proglucagon fragment.
我们使用特异性放射免疫分析法和分析凝胶过滤法，研究了非胰岛素依赖型糖尿病患者（NIDDM）和体重匹配的对照组在空腹状态下、静脉注射精氨酸后以及口服葡萄糖负荷后血浆中胰高血糖素原（PG）加工的主要产物。在空腹状态下，与对照组相比，NIDDM组中胰高血糖素样肽-1（GLP-1）免疫反应性显著升高。静脉注射精氨酸后和口服葡萄糖负荷后，所测的所有免疫反应性部分的血浆浓度均升高。两组静脉注射精氨酸后的所有综合增量反应相同。口服葡萄糖后，与对照组相比，NIDDM组血浆中的胰岛素浓度较低，所有胰高血糖素原产物的浓度较高。凝胶过滤分析表明，精氨酸刺激了两组中胰高血糖素（PG 33-61）、主要胰高血糖素原片段（PG 72-158）以及可能的GLP-1（PG 72-107酰胺）的分泌，而口服葡萄糖刺激了肠降血糖素（PG 1-69）和肠促胰岛素激素肠GLP-1（PG 78-107酰胺）的分泌。糖尿病患者空腹状态下免疫反应性GLP-1水平升高主要是由于主要胰高血糖素原片段浓度增加。
