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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。简介：在纽约大学医学院的Holz博士的指导下，他的研究项目是寻找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一种促胰岛素激素的降血糖特性。这种激素是胰高血糖素样肽-1-(7-36)-酰胺（GLP-1），是一种由肠远端肠内分泌l细胞分泌的肽，当给2型糖尿病患者服用时，可以降低血糖浓度。GLP-1：治疗糖尿病的新方法GLP-1在内分泌胰腺中表现出许多重要的生物学作用。早先人们认识到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。最近人们认识到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，从而大大增加其数量。这种生长因子样的作用引起了人们的注意，因为它表明GLP-1可能不仅在2型糖尿病患者中刺激b细胞质量的增加，而且在1型（青少年发病）糖尿病患者中也可能如此。本研究的目的是首先开发一种方法来跟踪GLP对细胞代谢的调节。

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.