PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS AS STIMULATORS OF ENDOCRINE DIFFERENTIATION

摘要

This invention pertains to the discovery that inhibition of phosphatidylinositol 3-kinase (PI3K) in human fetal undifferentiated cells induces morphological and functional endocrine differentiation. This is associated with an increase in MRNA levels of insulin, glucagon, and somatostatin, as well as an increase in the insulin protein content and secretion response to secretagogues. Blockade of PI3K also increases the proportion of pluripotent precursor cells coexpressing multiple hormones and the total number of terminally differentiated cells originating from these precursor cells. In one embodiment, this invention thus rpov9des methods for endocrine differentiation in cultured cells.