Method for restoring glucose responsiveness to insulin secretion
AssigneeThe Regents of the University of California
InventorsAllan S. Pollock, Sylvia Christakos, Daphne Reddy
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Abstract
This invention comprises engineered cells that express a nucleic acid that encodes a calbindin molecule, and exhibit the ability to secrete insulin in a glucose-sensitive fashion. This invention also comprises an artificial tissue that, when implanted into recipients that do not secrete insulin in a glucose-sensitive fashion, imparts to the recipients the ability to secrete insulin in a glucose-sensitive fashion. The artificial tissue comprises engineered cells that express a nucleic acid that encodes a calbindin molecule and secrete insulin in a glucose-sensitive fashion, enclosed by a semipermeable porous matrix.
Claims19
An engineered cell that secretes insulin in a glucose-sensitive fashion and that expresses a drug sensitivity, wherein said cell expresses a first exogenous nucleic acid that encodes a calbindin molecule and a second exogenous nucleic acid that encodes a drug sensitivity, with the proviso that in the absence of said first exogenous nucleic acid that encodes a calbindin molecule, the host cell does not secrete insulin in glucose-sensitive fashion.
An engineered cell that secretes insulin in a glucose-sensitive fashion, wherein said cell expresses an exogenous nucleic acid that encodes a calbindin molecule, with the proviso that in the absence of said first exogenous nucleic acid that encodes a calbindin molecule, the host cell does not secrete insulin in glucose-sensitive fashion, and with the additional proviso that the host cell may not be a rat insulinoma cell.
A method for imparting glucose-sensitive insulin secretion to a host cell that does not exhibit glucose-sensitive insulin secretion, comprising the steps of:
- a) providing a cell that is capable of producing and secreting insulin, but has an impaired ability to secrete insulin in a glucose sensitive fashion;
- b) stably transducing said cell with a nucleic acid that encodes a calbindin molecule and optionally with a nucleic acid that encodes a drug sensitivity, wherein the expression of said nucleic acid that encodes a calbindin molecule imparts to the engineered cell the enhanced ability to secrete insulin in a glucose-sensitive fashion.
A method of treating a mammal having an impaired ability to secrete insulin in response to glucose, comprising stably introducing into said mammal an engineered cell that expresses an exogenous nucleic acid that encodes a calbindin molecule, wherein said expression of said exogenous nucleic acid that encodes a calbindin molecule imparts to the engineered cell line the enhanced ability to secrete insulin in glucose-sensitive fashion.
A composition comprising
- a) an engineered cell that secretes insulin in a glucose-sensitive fashion, wherein said cell expresses an exogenous nucleic acid that encodes a calbindin molecule, with the proviso that in the absence of said exogenous nucleic acid that encodes a calbindin molecule, the host cell does not secrete insulin in glucose-sensitive fashion, and
- b) a semipermeable composition that encloses the engineered cell.
Dependencies are inferred from the claim text.