POLYPYRIMIDINE TRACT BINDING PROTEIN PROMOTES INSULIN SECRETORY GRANULE BIOGENESIS

摘要

The present invention relates to a method for stimulating production of secretory granules in peptide hormone-­secreting endocrine cells or neurons comprising the step of promoting the presence of polypyrimidine tract binding protein (PTB) or a biologically active fragment or derivative thereof in the cytoplasm of said cells or neurons. Preferably, the method alternatively or further comprises promoting the activity of PTB or said biologically active fragment or derivative thereof in the cytoplasm of said cells or neurons. It is also preferred that said promotion comprises the promotion of the nucleocytoplasmic transport of PTB. In another aspect, the invention relates to a method of screening for an agent capable of stimulating production of secretory granules in peptide hormone­-secreting endocrine cells or neurons comprising the steps of (a) contacting a cell capable of forming secretory granules and expressing polypyrimidine tract binding protein (PTB) or a biologically active fragment or derivative thereof with one or more compounds; and (b) assessing whether said one or more compounds promote the presence or activity of said polypyrimidine tract binding protein (PTB) or said biologically active fragment or derivative thereof in the cytoplasm of said cell. Comprised by the invention are further methods of screening for an agent useful as a cure for diabetes, sleeping disorders or depression as well as various medical uses of an agent capable of the promotion/reduction of the presence or activity of polypyrimidine tract binding protein (PTB) or of a biologically active fragment or derivative thereof. In alternative embodiments, the reduction or downregulation of PTB or said biologically active fragment or derivative thereof is considered.