Method for preventing and treating diabetes using neurturin

A method for stimulating and/or inducing the differentiation of insulin-producing cells from progenitor cells comprising contacting said progenitor cells with a neurturin product;

• wherein said neurturin product comprises a biologically active neurturin polypeptide;
• wherein said biologically active neurturin polypeptide is capable of dimerizing with another neurturin polypeptide and activating RET signaling;
• and wherein said biologically active neurturin polypeptide shares at least 90% sequence identity with:
• a) the human neurturin precursor protein having the amino acid sequence set forth in SEQ ID NO:
• 7;
• or
• b) the mature neurturin protein product that results from the cleavage of the human neurturin protein precursor having an amino acid sequence set forth in SEQ ID NO:
• 7.

A method for normalizing blood glucose levels in a mammal having impaired beta-cell function, comprising the step of:

• administering a neurturin product to said mammal in an amount sufficient to increase neurturin concentration relative to an untreated mammal having impaired beta-cell function, wherein the levels of blood glucose are normalized in said mammal administered the neurturin product;
• wherein the neurturin product comprises a biologically active neurturin polypeptide;
• wherein the biologically active neurturin polypeptide is capable of dimerizing with another neurturin polypeptide and activating RET signaling;
• and wherein the biologically active neurturin polypeptide shares at least 90% sequence identity with:
• a) the human neurturin precursor protein having the amino acid sequence set forth in SEQ ID NO:
• 7;
• or
• b) the mature neurturin protein product that results from the cleavage of the human neurturin protein precursor having an amino acid sequence set forth in SEQ ID NO:
• 7.

A method for generating insulin-producing cells from progenitor cells comprising the steps of:

• a) obtaining embryonic stem (ES) cells expressing a Pax4 gene;
• and
• b) culturing said Pax4-expressing ES cells in the presence of a neurturin product, wherein said neurturin product comprises a biologically active neurturin polypeptide;
• wherein said biologically active neurturin polypeptide is capable of dimerizing with another neurturin polypeptide and activating RET signaling;
• and wherein said biologically active neurturin polypeptide shares at least 90% sequence identity with:
• i) the human neurturin precursor protein having the amino acid sequence set forth in SEQ ID NO:
• 7;
• or
• ii) the mature neurturin protein product that results from the cleavage of the human neurturin protein precursor having an amino acid sequence set forth in SEQ ID NO:
• 7;
• wherein culturing said Pax-4 expressing ES cells in the presence of said neurturin product stimulates and/or induces differentiation of insulin-producing cells.

A method for generating insulin-producing cells from progenitor cells, comprising the steps of:

• a) contacting cells that express a pancreatic gene with a neurturin product;
• wherein the neurturin product comprises a biologically active neurturin polypeptide;
• wherein the biologically active neurturin polypeptide is capable of dimerizing with another neurturin polypeptide and activating RET signaling;
• and wherein the biologically active neurturin polypeptide shares at least 90% sequence identity with:
• i) the human neurturin precursor protein having the amino acid sequence set forth in SEQ ID NO:
• 7;
• or
• ii) the mature neurturin protein product that results from the cleavage of the human neurturin protein precursor having an amino acid sequence set forth in SEQ ID NO:
• 7;
• and
• b) culturing said pancreatic gene-expressing cells in the presence of said neurturin product;
• wherein culturing said pancreatic gene-expressing cells in the presence of said neurturin product stimulates and/or induces differentiation of insulin-producing cells.