Irs modulators

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, insuling 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 - 16 .(canceled) 
     
     
         17 . A method of identifying a compound that enhances insulin receptor substrate 2 (IRS2)-mediated signal transduction which comprises:
 a) providing a test cell which overproduces IRS2 and exhibits an increase in binding of an IRS2-binding protein to IRS2, relative to a control cell which produces IRS2 at a lower level, or does not produce the protein at all, and which exhibits a lesser amount of binding of said protein to IRS2;   b) contacting the compound with IRS2 or a complex comprising IRS2 and an IRS2-binding protein in the cell; and   c) examining the test cell for modulation of an IRS2-mediated cellular signal, wherein the modulation is greater in the test cell as compared to the control cell, thereby identifying the compound enhances IRS2-mediated signal transduction.   
     
     
         18 . A method of identifying a compound that upregulates insulin receptor substrate 2 (IRS2) function which comprises:
 a) providing a test cell which overproduces IRS2 and exhibits an increase in binding of an IRS2-binding protein to IRS2, relative to a control cell which produces IRS2 at a lower level, or does not produce the protein at all, and which exhibits a lesser amount of binding of said protein to IRS2;   b) causing the compound to come into contact with IRS2 or a complex comprising IRS2 and an IRS2-binding protein in the cell; and   c) examining the test cell for modulation of an IRS2-mediated cellular signal, wherein the modulation is greater in the test cell as compared to the control cell, thereby identifying that the compound upregulates IRS2.   
     
     
         19 . A method of enhancing insulin receptor substrate 2 (IRS2)-mediated signal transduction by activating IRS2. 
     
     
         20 . A method of treating a disease characterized by reduced or insufficient signaling through insulin receptor substrate 2 (IRS2) comprising upregulating IRS2 function.