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

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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.