Methods for identifying compounds for treating diabetes mellitus

Abstract

The invention is directed to methods for identifying candidate beta cell-sensitizing compounds comprising providing a pancreatic beta islet cell population derived from a diabetic subject, contacting the beta islet cell population with one or more somatostatin receptor 5-binding compounds, and identifying those somatostatin receptor 5-binding compounds that promote insulin secretion from the pancreatic beta islet cell population at a higher rate than from a control cell population. The invention is further directed to methods for treating type II diabetes comprising administering a beta cell-sensitizing compound identified by the first method of the invention to a diabetic patient in need of treatment.

1 . A method for identifying candidate pancreatic beta cell-sensitizing compounds comprising: 
 (a) providing a pancreatic beta-islet cell population derived from a diabetic subject, wherein the pancreatic beta islet cell population comprises pancreatic beta islet cells expressing somatostatin receptor 5;    (b) contacting the pancreatic beta-islet cell population with one or more somatostatin receptor 5-binding test compounds; and    (c) identifying those somatostatin receptor 5 binding test compounds that promote insulin secretion from the pancreatic beta-islet cell population at a higher rate than from a control cell population, wherein such compounds are candidate pancreatic beta cell-sensitizing compounds.    
     
     
         2 . The method of  claim 1 , wherein the somatostatin receptor 5-binding test compounds are somatostatin receptor 5 antagonists.  
     
     
         3 . The method of  claim 1 , wherein the contacting of the pancreatic beta-islet cell population is performed at an elevated glucose concentration.  
     
     
         4 . The method of  claim 3 , wherein the control cell population comprises pancreatic beta cells from a normoglycemic subject.  
     
     
         5 . The method of  claim 1 , further comprising: 
 (d) testing the pancreatic beta cell-sensitizing compounds for somatostatin receptor 2 agonist activity.    
     
     
         6 . The method of  claim 1  further comprising synthesizing the candidate pancreatic beta cell-sensitizing compounds.  
     
     
         7 . A method for treating type II diabetes, comprising administering to a diabetic patient in need of treatment a beta cell-sensitizing compound identified by the method of  claim 1  in an amount sufficient to improve glycemic control in the patient.  
     
     
         8 . The method of  claim 7 , further comprising administering a somatostatin receptor 2 agonist to the diabetic patient.  
     
     
         9 . The method of  claim 7 , wherein the beta cell-sensitizing compound comprises both somatostatin receptor 5 antagonist activity and somatostatin receptor 2 agonist activity.