Methods and compositions for in vivo induction of pancreatic beta cell formation
AssigneeBoard of Regents, The University of Texas System
InventorsBruno Doiron, Ralph A. DeFronzo
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Abstract
Embodiments of the invention stimulate three levels of beta cell physiology: (i) glucose metabolism, (ii) membrane receptor function, and (iii) transcriptional factors that result in the in vivo formation of beta cells in the pancreas for the purpose of treating diabetes. In certain aspects, the methods include the integration of three levels of cellular physiology: metabolism, membrane receptor function, and gene transcription. The integration of multiple levels of cellular physiology produces a synergistic effect on beta cell formation.
Claims24
A method for inducing formation of insulin-producing cells in a pancreas in vivo or in pancreatic cells in vitro comprising:
- providing a pancreas cell or pancreatic tissue comprising a pancreatic cell with a combination of (i) a first agent that increases glucokinase (GK) levels, (ii) a second agent that increases tyrosine receptor kinase activity and/or tyrosine kinase associated receptor activity, and (iii) a third agent that increases Pdx-1 mediated transcription, wherein the pancreas cell transdifferentiates to an insulin-producing cell.
A method for inducing formation of an insulin-producing cell from pancreatic cells in vivo comprising:
- providing to a pancreas in vivo, a combination of (i) a first agent that increases glucokinase (GK) levels, (ii) a second agent that increases tyrosine receptor kinase activity and/or tyrosine kinase associated receptor activity, and (iii) a third agent that increases Pdx-1 mediated transcription in pancreatic cells, wherein the pancreatic cell is transformed to an insulin-producing cell.
A method of treating diabetes comprising:
- providing a therapeutic composition to a pancreas in vivo comprising (i) glucokinase expression cassette configured to express a functional glucokinase protein in a pancreatic cell, (ii) a tyrosine phosphatase 1B inhibitor, and (iii) a Pdx-1 expression cassette configured to express a functional Pdx-1 protein in a pancreatic cell, wherein pancreatic beta cells are induced in the pancreas and provide insulin to treat diabetes.
Dependencies are inferred from the claim text.