Buhl T, Thim L, Kofod H, Orskov C, Harling H, Holst J J
Institute of Medical Physiology C, Panum Institute, Copenhagen, Denmark.
J Biol Chem. 1988 Jun 25;263(18):8621-4.
Recent studies have revealed that the glucagon gene is expressed in the mammalian intestine. Here it codes for "glicentin" (proglucagon 1-69) and a glucagon-like peptide, proglucagon 78-107, recently isolated from porcine intestine. We studied the fate of the remaining COOH-terminal part of proglucagon (proglucagon 111-160) using radioimmunoassays against proglucagon 111-123 and 126-160. Two peptides were isolated from acid ethanol extracts of porcine ileal mucosa and sequenced: one corresponding to proglucagon 126-158 and one probably corresponding to proglucagon 111-158. By comparing human and porcine proglucagon sequences, Ala117 is replaced by Thr, and Ile138, Ala144, Ile152 and Gln153 are replaced by Val, Thr, Leu, and His. By gel filtration and radioimmunoassay of intestinal extracts it was established that a large part of porcine and virtually all of human proglucagon are processed to release proglucagon 111-123 (designated spacer peptide 2), which, like proglucagon 126-158 must be considered a potential hormonal entity. By isocratic high pressure liquid chromatography human spacer peptide 2 was indistinguishable from synthetic proglucagon 111-122 amide, suggesting that this is the structure of the naturally occurring human peptide.
最近的研究表明，胰高血糖素基因在哺乳动物肠道中表达。在这里，它编码“肠高血糖素”（胰高血糖素原1 - 69）和一种类胰高血糖素肽，即最近从猪肠道中分离出的胰高血糖素原78 - 107。我们使用针对胰高血糖素原111 - 123和126 - 160的放射免疫分析法，研究了胰高血糖素原剩余的COOH末端部分（胰高血糖素原111 - 160）的去向。从猪回肠黏膜的酸性乙醇提取物中分离出两种肽并进行测序：一种对应于胰高血糖素原126 - 158，另一种可能对应于胰高血糖素原111 - 158。通过比较人和猪的胰高血糖素原序列，发现丙氨酸117被苏氨酸取代，异亮氨酸138、丙氨酸144、异亮氨酸152和谷氨酰胺153分别被缬氨酸、苏氨酸、亮氨酸和组氨酸取代。通过对肠道提取物进行凝胶过滤和放射免疫分析，确定猪的大部分以及几乎所有的人胰高血糖素原都被加工释放出胰高血糖素原111 - 123（称为间隔肽2），它与胰高血糖素原126 - 158一样，必须被视为一种潜在的激素实体。通过等度高压液相色谱法，人间隔肽2与合成的胰高血糖素原111 - 122酰胺无法区分，这表明这就是天然存在的人肽的结构。
