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AssigneeThe Trustees of Columbia University in the City of New York
InventorsDomenico Accili, Ryotaro Bouchi
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Disclosed herein are methods involving the targeting of 5HT biosynthesis in gut insulin-negative cells to convert them into insulin-positive cells. Also, disclosed are methods for treating a disease or disorder in a mammal, preferably a human, associated with impaired pancreatic endocrine function, by administering a therapeutically effective amount of an enumerated active agent that reduces the expression, biosynthesis, signaling or biological activity of serotonin or increases its degradation, wherein administering comprises delivering the agent to Gut Ins− cells in the mammal. Other embodiments of the method are directed to therapy wherein an agent that significantly reduces FOXO1 expression, biosynthesis, signaling or biological activity or increases its degradation is administered in addition to the agent that reduces serotonin, or alternatively an agent that reduces FOXO1 expression is targeted to serotonin-positive gut enteroendocrine cells.
A method comprising administering to a mammal having a disease or disorder associated with impaired pancreatic endocrine function, a therapeutically effective amount of a nucleic acid encoding a dominant-negative form of FOXO1, wherein administering comprises delivering the nucleic acid to Gut Ins− cells whereby expression of the nucleic acid products produces Gut Ins+ cells that make and secrete biologically active insulin thereby treating the disease or disorder, wherein administering targets serotonin-positive enteroendocrine cells.
A method for producing Gut Ins+ cells in the gut of a mammal that make and secrete biologically active insulin, comprising administering to the mammal a nucleic acid encoding a dominant-negative form of FOXO1 thereby reducing the expression, biosynthesis, signaling or biological activity of endogenous FOXO1, wherein administering comprises delivering the agent to Gut Ins− cells and wherein expression of the nucleic acid products produces Gut Ins+ cells that make and secrete biologically active insulin, wherein the administering targets serotonin positive enteroendocrine cells.
Dependencies are inferred from the claim text.