Ribosomal Remodeling in Diabetes
AssigneeJoslin Diabetes Center, Inc.
InventorsJean Schaffer, Abigael Cheruiyot
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Abstract
This disclosure relates to ribosomal remodeling due to high glucose conditions. In some embodiments, translation of proteins in pancreatic beta-cells is altered based on the ribosomal remodeling. Means of increasing the percentage of large ribosomal subunit protein P1 (RPLP1) associated with ribosomes and/or decreasing the percentage of soluble RPLP1 in a cell to counteract effects of high glucose conditions in diabetes are disclosed.
Claims26
A method of treating or preventing diabetes in a subject in need thereof comprising increasing the percentage of ribosome-associated RPLP1 or decreasing the percentage of soluble RPLP1 in a cell of the subject comprising:
- a. phosphorylating RPLP1,
- b. inhibiting dephosphorylation of RPLP1, and/or
- c. expressing an RPLP1 mutant comprising one or more phosphomimetic amino acids,
- thereby increasing the percentage of ribosome-associated RPLP1 and/or decreasing the percentage of soluble RPLP1 in the subject and treating or preventing diabetes.
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A method of treating or preventing diabetes in a subject in need thereof comprising:
- a. preparing iPSCs and/or pancreatic-beta-cells in vitro;
- b. treating said iPSCs or pancreatic beta-cells with an agent for gene editing of RPLP1, wherein the gene editing causes expression of an RPLP1 mutant comprising one or more phosphomimetic amino acids in the cell;
- and
- c. transplanting the treated iPSCs or pancreatic beta-cells into the subject, wherein the transplanting increases insulin levels in the subject and/or decreases glucose levels in the subject.
A method of reducing the incidence of hyperglycemia or immune attack on pancreatic beta-cells in a subject in need thereof comprising:
- a. preparing iPSCs and/or pancreatic-beta-cells in vitro;
- b. treating said iPSCs or pancreatic beta-cells with an agent for gene editing of RPLP1, wherein the gene editing causes expression of an RPLP1 mutant comprising one or more phosphomimetic amino acids in the cell;
- and
- c. transplanting the treated iPSCs or pancreatic beta-cells into the subject, wherein the transplanting increases insulin levels in the subject and/or decreases glucose levels in the subject.
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Dependencies are inferred from the claim text.