Garber Alan J
Department of Medicine, Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Diabetes Obes Metab. 2005 Nov;7(6):666-74. doi: 10.1111/j.1463-1326.2005.00457.x.
Rapid-acting genetically engineered insulin analogues emerging in the last 10 years are now established as more effective prandial insulins than traditional short-acting human insulin. The development of analogues for use as basal insulin, however, has been much slower. Methods of pro-tracting the time-action curve of injected insulin include complexing with proteins, insulin crystal formation, shifting the iso-electric point of the amino acid sequence or attaching a fatty-acid side chain to the molecule. The latter two methods have been more successful in producing physiologic insulin profiles when compared with the former methods. The principle of acylation has also been applied to prolong the action of other hormones, such as glucagon-like peptide 1 (GLP-1), as the native peptide has a very short half-life. Preliminary results with this compound and other GLP-1 analogues show promise in treating patients with type 2 diabetes. In summary, the development of new insulin and other hormone preparations by the manipulation of native peptide structure has recently improved our antidiabetic armamentarium, and further research will continue this fruitful approach.
在过去10年中出现的速效基因工程胰岛素类似物，现已被确立为比传统短效人胰岛素更有效的餐时胰岛素。然而，用作基础胰岛素的类似物的开发则要慢得多。延长注射胰岛素作用时间曲线的方法包括与蛋白质复合、胰岛素晶体形成、改变氨基酸序列的等电点或在分子上连接脂肪酸侧链。与前两种方法相比，后两种方法在产生生理性胰岛素谱方面更为成功。酰化原理也已应用于延长其他激素的作用，如胰高血糖素样肽1（GLP-1），因为天然肽的半衰期很短。该化合物和其他GLP-1类似物的初步结果显示出治疗2型糖尿病患者的前景。总之，通过操纵天然肽结构来开发新的胰岛素和其他激素制剂，最近改善了我们的抗糖尿病药物库，进一步的研究将继续采用这种富有成效的方法。
