Methods of upregulating irs function

Abstract

This invention is directed to a general method for the chronic treatment, potential cure, or prevention of various metabolic and related diseases in people, including diabetes, by modulating IRS2 activity in cells and tissues in the body. IRS1 and IRS2 are part of the insulin or insulin-like growth factor signaling pathway. By upregulating the levels or functional activity of IRS2, insulin is used more efficiently by the body to control nutrient levels. By upregulating IRS2 levels or functional activity in pancreatic β-cells, glucose sensing and insulin secretion are enhanced.

1 - 17 . (canceled) 
     
     
         18 . A method of restoring or enhancing insulin sensitivity in a cell comprising upregulating IRS2 function. 
     
     
         19 . A method of restoring or enhancing pancreatic β-cell function comprising upregulating IRS2 function. 
     
     
         20 . A method of treating a disease characterized by reduced or insufficient signaling through IRS2 comprising upregulating IRS2 function. 
     
     
         21 . The method of  claim 20 , wherein the disease is a metabolic disease. 
     
     
         22 . The method of  claim 20 , wherein the disease is diabetes. 
     
     
         23 . The method of  claim 20 , wherein the disease is obesity. 
     
     
         24 . The method of  claim 20 , wherein the disease is female infertility. 
     
     
         25 . The method of  claim 20 , wherein the disease is a central nervous system disorder. 
     
     
         26 . The method of  claim 18 , wherein the upregulation of IRS2 function comprises activation of IRS2. 
     
     
         27 . The method of  claim 18 , wherein the upregulation of IRS2 function comprises activation of a dimeric or multimeric complex that includes IRS2. 
     
     
         28 . The method of  claim 27 , wherein the complex further includes a tyrosine kinase receptor or an SH 2  domain containing protein. 
     
     
         29 . The method of  claim 18 , wherein the upregulation of IRS2 function comprises inhibition of phosphorylation of carboxy terminal serine residues of IRS2. 
     
     
         30 . The method of  claim 18 , wherein the upregulation of IRS2 function comprises enhanced expresssion of IRS2. 
     
     
         31 . The method of  claim 18 , wherein the upregulation of IRS2 function comprises inhibition of degradation of IRS2. 
     
     
         32 . The method of  claim 18 , wherein the upregulation of IRS2 activity comprises specifically enhancing interaction between IRS2 and an IRS2 binding partner selected from the group consisting of 14-3-3, pini, a protein kinase C isoform, a protein kinase B isoform, Tor kinase, Jnk1, and an SH 2  domain comprising protein.