SOGA polynucleotides and polypeptides and uses thereof
View Patent ↗The present invention relates to the identification of polynucleotides and polypeptides involved in insulin and adiponectin signaling and regulation of glucose production. The invention further relates to the use of the identified polynucleotides and polypeptides, and inhibitors of the polynucleotides and polypeptides, in the regulation of glucose production and the monitoring and treatment of metabolic disorders such as diabetes.
1. An antibody or antibody fragment that specifically binds to a polypeptide encoded by a polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising a nucleotide sequence at least 95% identical to a nucleotide sequence selected from the group consisting of SEQ ID NOS:1 and 3 and encoding a functional Suppressor of Glucose by Autophagy (SOGA) polypeptide;
(b) a polynucleotide encoding a functional SOGA polypeptide comprising an amino acid sequence at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NOS:2 and 4;
(c) a polynucleotide of (a) or (b) encoding a C-terminal functional fragment of a SOGA polypeptide of about 80 kDa; and
(d) a polynucleotide of (a) or (b) encoding a C-terminal functional fragment of a SOGA polypeptide of about 25 kDa.
2. The antibody or antibody fragment of claim 1 , wherein said polynucleotide is selected from the group consisting of:
(a) a polynucleotide comprising a nucleotide sequence selected from the group consisting of SEQ ID NOS:1 and 3;
(b) a polynucleotide encoding a functional SOGA polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:2 and 4;
(c) a polynucleotide of (a) or (b) encoding a C-terminal functional fragment of a SOGA polypeptide of about 80 kDa;
(d) a polynucleotide of (a) or (b) encoding a C-terminal functional fragment of a SOGA polypeptide of about 25 kDa; and
(e) a polynucleotide comprising a nucleotide sequence that differs from the nucleotide sequences of any of (a) to (d) above due to the degeneracy of the genetic code.
3. The antibody or antibody fragment of claim 1 , wherein the polynucleotide encodes a C-terminal functional fragment of a SOGA polypeptide of about 80 kDa.
4. The antibody or antibody fragment of claim 1 , wherein the polynucleotide encodes a C-terminal functional fragment of a SOGA polypeptide of about 25 kDa.
5. The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment is a polyclonal antibody or antibody fragment.
6. The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment is a monoclonal antibody or antibody fragment.
7. The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment specifically binds to a human SOGA polypeptide.
8. An antibody or antibody fragment that specifically recognizes an epitope within the amino acid sequence STQSLTSCFARSSRSAIRHSPSKC (SEQ ID NO:5).
9. The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment specifically binds to a mouse SOGA polypeptide.
10. An antibody or antibody fragment that specifically recognizes an epitope within the amino acid sequence CSAQSLASCFIRPSRN (SEQ ID NO:6) or SAQSLASCFIRPSRNPIRHSPSKC (SEQ ID NO:7).
11. A pharmaceutical composition comprising the antibody or antibody fragment of claim 1 and a pharmaceutically acceptable carrier.
12. A kit comprising the antibody or antibody fragment of claim 1 .
13. A method of increasing glucose production in a cell in vitro comprising contacting said cell with the antibody or antibody fragment of claim 1 in an amount effective to increase glucose production in said cell.
14. A method of increasing autophagy in a cell in vitro comprising contacting said cell with the antibody or antibody fragment of claim 1 in an amount effective to increase autophagy in said cell.