Kofod H, Unson C G, Merrifield R B
Hagedorn Research Laboratory, Gentofte, Denmark.
Int J Pept Protein Res. 1988 Dec;32(6):436-40. doi: 10.1111/j.1399-3011.1988.tb01374.x.
Glucagon and secretin and some of their hybrid analogs potentiate glucose-induced release of insulin from isolated mouse pancreatic islets. It was recently shown that the synthetic glucagon analog, desHis1[Glu9]glucagon amide, does not stimulate the formation of cyclic adenosine monophosphate in the rat hepatocyte membrane, but binds well to the glucagon receptor and is a good competitive antagonist of glucagon. In the present study the effect of this analog on isolated islets was examined. desHis1-[Glu9]glucagon amide at 3 x 10(-7) M, in the presence of 0.01 M D-glucose, increased the release of insulin by 30% and maintained that level for the full 30-min test period. The rate of insulin release returned to the glucose-induced base line after removal of the peptide. The same insulin level was produced by 3 x 10(-9) M glucagon, and at 3 x 10(-7) M glucagon insulin release was enhanced 290% above the glucose base line.
胰高血糖素、促胰液素及其一些杂合类似物可增强葡萄糖诱导的离体小鼠胰岛释放胰岛素。最近的研究表明,合成的胰高血糖素类似物去组氨酸1[谷氨酸9]胰高血糖素酰胺不会刺激大鼠肝细胞膜中环磷酸腺苷的形成,但能很好地与胰高血糖素受体结合,是一种良好的胰高血糖素竞争性拮抗剂。在本研究中,检测了这种类似物对离体胰岛的作用。在存在0.01 M D-葡萄糖的情况下,3×10(-7) M的去组氨酸1-[谷氨酸9]胰高血糖素酰胺使胰岛素释放增加了30%,并在整个30分钟的测试期内维持该水平。去除该肽后,胰岛素释放速率恢复到葡萄糖诱导的基线水平。3×10(-9) M的胰高血糖素产生相同的胰岛素水平,而在3×10(-7) M的胰高血糖素作用下,胰岛素释放比葡萄糖基线水平提高了290%。