Egan Josephine M, Bulotta Angela, Hui Hongxiang, Perfetti Riccardo
Diabetes Section, National Institute on Aging, NIH, Baltimore, MD, USA.
Diabetes Metab Res Rev. 2003 Mar-Apr;19(2):115-23. doi: 10.1002/dmrr.357.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that, when given exogenously, is capable of normalizing blood glucose in individuals with type 2 diabetes. Until recently most of the research on this compound had been related to its insulinotropic properties. However, GLP-1 also regulates insulin synthesis and proinsulin gene expression, as well as the components of the glucose-sensing machinery. In addition to regulating insulin release, it is involved in regulating the secretion of at least two other islet hormones--glucagon and somatostatin. Extraislet effects of GLP-1 include a role in the central nervous system stress response, hypothalamic-pituitary function, and the suppression of gastric emptying. Recent studies from our own and other laboratories show that GLP-1 can regulate islet growth and is a differentiation factor of the endocrine pancreas. This leads us to propose that GLP-1 and GLP-1 receptor agonists, in the context of long-term treatment of type 2 diabetes, will have broader biological action on the endocrine pancreas than was earlier anticipated. We propose that GLP-1 is a growth factor for pancreatic endocrine cells and can increase islet cell mass. Here we review those reports that have highlighted its role as a factor for islet cell growth and differentiation.
胰高血糖素样肽-1(GLP-1)是一种肠促胰岛素激素,外源性给予时能够使2型糖尿病患者的血糖恢复正常。直到最近,关于这种化合物的大多数研究都与其促胰岛素特性有关。然而,GLP-1还调节胰岛素合成和胰岛素原基因表达,以及葡萄糖感应机制的组成部分。除了调节胰岛素释放外,它还参与调节至少另外两种胰岛激素——胰高血糖素和生长抑素的分泌。GLP-1的胰岛外作用包括在中枢神经系统应激反应、下丘脑-垂体功能以及抑制胃排空中发挥作用。我们自己的实验室和其他实验室最近的研究表明,GLP-1可以调节胰岛生长,并且是内分泌胰腺的分化因子。这使我们提出,在2型糖尿病的长期治疗中,GLP-1和GLP-1受体激动剂对内分泌胰腺的生物学作用将比早期预期更为广泛。我们提出GLP-1是胰腺内分泌细胞的生长因子,并且可以增加胰岛细胞数量。在此,我们综述那些突出其作为胰岛细胞生长和分化因子作用的报告。