Gene products that regulate glucose response in cells
OwnerChristopher B. Newgard, Per Bo Jenseninventors
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Abstract
The present invention describes the identification of numerous genes, both known and unknown, that play an important role in the ability of cell to respond to glucose stimulation under physiologic conditions. These genes may be used to enhance, stabilize or introduce glucose-responsiveness in a host cell, in particular, a host cell that secretes insulin. In addition, these genes may be used as targets for drug screening and as diagnostic indicators for the loss of glucose-responsiveness.
Claims55
An isolated and purified polynucleotide encoding a polypeptide having an amino acid sequence encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74.
An expression cassette comprising (a) a polynucleotide encoding a polypeptide having an amino acid sequence encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 and 74 and (b) a promoter, wherein said polynucleotide is positioned so as to be under the regulatory control of said promoter.
An oligonucleotide of 15 to about 50 bases, comprising 15 or more consecutive bases of SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74, or the complement thereof.
A cell comprising a heterologous polynucleotide encoding a polypeptide having an amino acid sequence encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74.
A method of expressing a polypeptide comprising:
- (a) providing a host cell, said host cell comprising a heterologous an expression cassette comprising (a) a polynucleotide encoding a polypeptide having an amino acid sequence encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74 and (b) a promoter active in said host cell, wherein said polynucleotide is positioned so as to be under the regulatory control of said promoter;
- and
- (b) culturing said host cell under conditions supporting the expression of said polypeptide.
A polypeptide having an amino acid sequence encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74.
A peptide of 5 to about 35 residues comprising 5 or more consecutive residues of a polypeptide encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74.
A monoclonal antibody that binds immunologically to a polypeptide encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74.
A nucleic acid encoding single chain monoclonal antibody that binds immunologically to a polypeptide encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74.
A polyclonal antibody composition, antibodies of which bind immunologically to a polypeptide having an amino acid sequence encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74.
A method for modulating the glucose-responsiveness of a cell comprising introducing into said cell an expression cassette comprising (a) a polynucleotide encoding a polypeptide having an amino acid sequence encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74 and (b) a promoter active in said cell, wherein said polynucleotide is positioned so as to be under the regulatory control of said promoter.
A method of screening for a modulator of expression of a polypeptide encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74 comprising:
- (a) providing a cell that expresses a polypeptide encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74;
- (b) treating said cell with a candidate modulator;
- (c) determining the effect on expression of a polypeptide encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74, as compared to a similar cell not treated with said candidate modulator,
- wherein a difference between the expression in treated and untreated cells indicates that said candidate modulator is a modulator of expression of a polypeptide encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74.
A method for measuring the expression of a polypeptide encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74 in a cell comprising:
- (a) obtaining an mRNA population from said cell;
- (b) contacting said population with a DNA probe that hybridizes to SEQ ID NOS:1-7, or the complement thereof;
- and
- (c) measuring hybridization of said probe to members of said population,
- whereby measuring hybridization of said probe measures the expression of a polypeptide encoded by SEQ ID NOS:1-7, 66, 67, 69, 70, 72 or 74.
Dependencies are inferred from the claim text.