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, 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 .- 15 . (canceled) 
     
     
         16 . A method of determining whether a small molecule is an activator or an inhibitor of IRS2 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 small molecule to come into contact with the intact Test Cell;   c) measuring the amount of the IRS2 binding protein bound to IRS2.   
     
     
         17 . A method of identifying a small molecule capable of increasing the level of expression from an IRS2 promoter in a mammalian cell which comprises:
 a) providing a Test Cell which contains said IRS2 promoter operably linked to a reporter gene such that increased expression of the IRS2 promoter sequence using a substance known to be capable of upregulating the endogenous IRS2 gene results in an increase in reporter protein levels;   b) causing said small molecule to come into contact with the intact Test Cell, and   c) determining whether an increase in reporter protein level in the Test Cell has occurred.