Induction of beta cell differentiation in human cells
First Claim
1. A method for inducing insulin gene expression in cultured pancreatic cells, the method comprising the steps of:
- (i) expressing a recombinant NeuroD/BETA2 polynucleotide and a recombinant PDX-1 polynucleotide in pancreatic cells that have been cultured under conditions such that the pancreatic cells are in contact with other cells in the culture; and
(ii) contacting the cells with a GLP-1 receptor agonist, thereby inducing insulin gene expression in the pancreatic cells.
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Abstract
The present invention provides methods for inducing insulin gene expression in cultured pancreas cells, the method comprising contacting a culture of endocrine pancreas cells expressing a PDX-1 gene and a NeuroD/BETA2 gene with a GLP-1 receptor agonist, wherein the cells have been cultured under conditions such that the cells are in contact with other cells in the culture, thereby inducing insulin gene expression in the cells. The invention also provides high throughput screening methods for modulators of β-cell function, stable cultures of cells made by the methods of the invention, and methods of treating a human subject using the methods of the invention.
20 Citations
32 Claims
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1. A method for inducing insulin gene expression in cultured pancreatic cells, the method comprising the steps of:
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(i) expressing a recombinant NeuroD/BETA2 polynucleotide and a recombinant PDX-1 polynucleotide in pancreatic cells that have been cultured under conditions such that the pancreatic cells are in contact with other cells in the culture; and
(ii) contacting the cells with a GLP-1 receptor agonist, thereby inducing insulin gene expression in the pancreatic cells. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
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12. An endocrine pancreas β
- -cell comprising a recombinant PDX-1 polynucleotide and a recombinant NeuroD/BETA2 polynucleotide.
- View Dependent Claims (13, 14, 15, 16)
- 17. A stable culture of pancreatic cells, wherein the pancreatic cells are in contact with other cells in the culture and cultured as aggregates in suspension, wherein the pancreatic cells express a recombinant PDX-1 polynucleotide and a recombinant NeuroD/BETA2 polynucleotide, and wherein insulin gene expression is stimulated in the pancreatic cells when exposed to an effective amount of a GLP-1 receptor agonist.
- 24. A stable culture of pancreatic cells, wherein the pancreatic cells are in contact with other cells in the culture, wherein the pancreatic cells express a recombinant PDX-1 polynucleotide and a recombinant NeuroD/BETA2 polynucleotide, and wherein insulin gene expression is stimulated in the pancreatic cells when exposed to an effective amount of a GLP-1 receptor agonist, and wherein the pancreatic cells are β
Specification