THE MECHANISM OF ACTION OF A NEWLY DEVELOPED BLOOD GLUCOSE-LOWERING HORMONE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。介绍：在纽约大学医学院Holz博士指导下的研究项目中，他试图确定和描述可能用于治疗2型（成人发病）糖尿病的新治疗策略。为此，他专注于确定目前正在临床研究中的促胰岛素激素的降血糖特性。该激素是胰高血糖素样肽-1-（7-36）-酰胺（GLP-1），其是由远端肠的肠内分泌L细胞分泌的肽，并且当给予2型糖尿病受试者时，其降低血糖浓度。 GLP-1：糖尿病的新治疗方法。GLP-1在内分泌胰腺中表现出许多重要的生物学作用。早期认识到GLP-1刺激b细胞胰岛素基因转录、胰岛素原的翻译生物合成和葡萄糖依赖性胰岛素分泌。最近认识到的是，GLP-1也对b细胞发挥生长因子样作用。例如，GLP-1刺激啮齿动物b细胞的新生，从而显著增加其数量。这种生长因子样作用引起了人们的关注，因为它表明GLP-1可能不仅在2型糖尿病受试者中刺激b细胞质量增加，而且可能在1型（青少年发作）糖尿病受试者中也刺激b细胞质量增加。本研究的目的首先是开发一种通过GLP调节细胞代谢的方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: The research program under the direction of Dr. Holz at New York University School of Medicine is one in which he has sought to identify and characterize novel therapeutic strategies that might be of use for the treatment of type 2 (adult-onset) diabetes mellitus. To this end, he has focused on ascertaining the blood glucose-lowering properties of an insulinotropic hormone that is currently under clinical investigation. This hormone is glucagon-like peptide-1-(7-36)-amide (GLP-1), a peptide secreted by enteroendocrine L-cells of the distal intestine, and which when administered to type 2 diabetic subjects, lowers blood glucose concentration. GLP-1: A New Treatment for Diabetes Mellitus. GLP-1 exhibits a number of important biological actions at the endocrine pancreas. Earlier on it was recognized that GLP-1 stimulates b-cell insulin gene transcription, translational biosynthesis of proinsulin, and glucose-dependent insulin secretion. What has recently become appreciated is that GLP-1 also exerts growth factor-like effects on b-cells. For example, GLP-1 stimulates neogenesis of rodent b-cells, thereby increasing their number substantially. This growth factor-like action has attracted attention because it suggests that GLP-1 might stimulate an increase of b-cell mass not only in type 2 diabetic subjects, but perhaps in type 1 (juvenile-onset) diabetic subjects as well. The purpose of the proposed research is first to develop a method for following the modulation of cell metabolism by GLP.