McIntosh Christopher H S, Demuth Hans-Ulrich, Kim Su-Jin, Pospisilik J Andrew, Pederson Raymond A
University of British Columbia, Department of Cellular and Physiological Sciences, Vancouver, BC, Canada.
Int J Biochem Cell Biol. 2006;38(5-6):860-72. doi: 10.1016/j.biocel.2005.12.013. Epub 2006 Jan 11.
A number of alternative therapies for type 2 diabetes are currently under development that take advantage of the actions of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide on the pancreatic beta-cell. One such approach is based on the inhibition of dipeptidyl peptidase IV (DP IV), the major enzyme responsible for degrading the incretins in vivo. DP IV exhibits characteristics that have allowed the development of specific inhibitors with proven efficacy in improving glucose tolerance in animal models of diabetes and type 2 human diabetics. While enhancement of insulin secretion, resulting from blockade of incretin degradation, has been proposed to be the major mode of inhibitor action, there is also evidence that inhibition of gastric emptying, reduction in glucagon secretion and important effects on beta-cell differentiation, mitogenesis and survival, by the incretins and other DP IV-sensitive peptides, can potentially preserve beta-cell mass, and improve insulin secretory function and glucose handling in diabetics.
目前正在研发多种用于治疗2型糖尿病的替代疗法，这些疗法利用了肠促胰岛素激素胰高血糖素样肽-1和葡萄糖依赖性促胰岛素多肽对胰腺β细胞的作用。其中一种方法是基于抑制二肽基肽酶IV（DP IV），它是体内负责降解肠促胰岛素的主要酶。DP IV具有一些特性，这使得能够开发出在糖尿病动物模型和2型人类糖尿病患者中已证实具有改善糖耐量功效的特异性抑制剂。虽然有人提出，因阻断肠促胰岛素降解而导致的胰岛素分泌增强是抑制剂作用的主要方式，但也有证据表明，肠促胰岛素和其他DP IV敏感肽对胃排空的抑制、胰高血糖素分泌的减少以及对β细胞分化、有丝分裂和存活的重要影响，可能会维持β细胞数量，并改善糖尿病患者的胰岛素分泌功能和葡萄糖处理能力。
