Novel Target for Diagnosis and Treatment of Diabetes and Cardiovascular Diseases

Abstract

Diagnostic, prognostic, and treatment methods, compositions, and kits for enhancing insulin secretion and beta cell numbers and functions, and controlling glycemia associated with diabetes, obesity, atherosclerosis, stroke, myocardial infarction, and other cardiovascular diseases, by modulating FKN/CX3CR1 expression levels or activities, and its downstream signaling pathways in a subject in need or at risk.

What is claimed is: 
     
         1 . A method for increasing insulin secretion and controlling glycemia comprising administering to a subject in need thereof an effective amount of a composition comprising an agent that activates FKN/CX3CR1 or downstream signaling pathways. 
     
     
         2 . The method of  claim 1 , wherein said agent is soluble FKN, or an analog thereof. 
     
     
         3 . The method of  claim 1 , wherein said agent is a CX3CR1 agonist. 
     
     
         4 . The method of  claim 1 , wherein said agent enhances CX3CR1 or FKN expression or activity in said subject. 
     
     
         5 . The method of  claim 1 , wherein said agent enhances FKN/CX3CR1 downstream signaling pathways. 
     
     
         6 . The method of  claim 1 , wherein said agent increases beta cell numbers, improves pancreatic islet function, or decreases blood glucose level in said subject. 
     
     
         7 . The method of  claim 1 , wherein said agent reduces plaqability of macrophages to atherosclerotic lesions. 
     
     
         8 . The method of  claim 1 , wherein said method is used for preventing or treating disorders selected from the group consisting of diabetes, obesity, atherosclerosis, stroke, myocardial infarction, and cardiovascular diseases. 
     
     
         9 . A pharmaceutical composition for increasing insulin secretion and controlling glycemia comprising a pharmaceutically acceptable excipient and an effective amount of an agent that activates FKN/CX3CR1 or downstream signaling pathways. 
     
     
         10 . The composition of  claim 9 , wherein said agent is soluble FKN, or an analog thereof. 
     
     
         11 . The composition of  claim 9 , wherein said agent is a CX3CR1 agonist. 
     
     
         12 . The composition of  claim 9 , wherein said agent enhances CX3CR1 or FKN expression or activity in said subject. 
     
     
         13 . The composition of  claim 9 , wherein said agent enhances FKN/CX3CR1 downstream signaling pathways. 
     
     
         14 . The composition of  claim 9 , said agent increases beta cell numbers, improves pancreatic islet function, or decreases blood glucose level in said subject. 
     
     
         15 . The method of  claim 9 , wherein said agent reduces plaqability of macrophages to atherosclerotic lesions. 
     
     
         16 . The method of  claim 9 , wherein said agent is used for preventing or treating disorders selected from the group consisting of diabetes, obesity, atherosclerosis, stroke, myocardial infarction, and cardiovascular diseases. 
     
     
         17 . A diagnostic method for insulin secretion deficiency, beta cell dysfunction, or glycemia, comprising:
 (a) obtaining a biological sample from a subject at risk;   (b) determining in the sample an expression level or activity of CX3CR1 or FKN, and   (c) diagnosing said subject as at risk for insulin secretary deficiency or beta cell dysfunction when the expression level or activity of CX3CR1 or FKN in said subject is significantly decreased or reduced as compared to an expression level or activity of CX3CR1 or FKN in a normal subject.   
     
     
         18 . A method for determining a prognosis of a subject having insulin secretion deficiency, beta cell dysfunction, or glycemia, comprising:
 (a) obtaining a biological sample of said subject;   (b) determining the expression level or activity of CX3CR1 or FKN in a sample from said subject before and after a treatment; and   (c) associating a lower relative CX3CR1 or FKN expression level or activity with a higher risk course of insulin secretion deficiency, beta cell dysfunction, or glycemia, thereby determining the prognosis of the subject.