Gfi1 inhibitors for the treatment of hyperglycemia

Abstract

The present invention relates to methods and pharmaceutical compositions useful for the treatment of hyperglycemia. Thorough multiple analyses, inventors demonstrated that Gfi1 is expressed in pancreatic acinar cells, starting from the first stages of pancreatic embryonic development. Furthermore, they observed that Gfi1 mRNA levels remain steady throughout embryonic development, while they significantly increase during the first days of life. They challenged conditional mutant mice with high fat diet for 5 months and monitored their weight and glycemia weekly. All the animals displayed a rapid increase in body mass as expected. While control mice rapidly developed a massive hyperglycemia, mutant mice remained normoglycemic throughout the entire experiment. A similar protection from induced diabetes was observed upon treatment with a high dose of Streptozotocin. Accordingly, the present invention relates to a method of treating hyperglycemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an inhibitor of Gfi1.

1 . A method of treating hyperglycemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an inhibitor of Gfi1. 
     
     
         2 . The method of  claim 1  wherein the subject suffers from diabetes. 
     
     
         3 . The method of  claim 1  wherein the subject suffers from Type 1 diabetes mellitus. 
     
     
         4 . The method of  claim 1  wherein the subject suffers from type 2 diabetes. 
     
     
         5 . The method of  claim 1  wherein the inhibitor is an antisense oligonucleotide. 
     
     
         6 . The method of  claim 1  wherein the inhibitor is a small molecule. 
     
     
         7 . The method of  claim 6  wherein the small molecule is T-3775440. 
     
     
         8 . The method of  claim 1  wherein the inhibitor is a siRNA. 
     
     
         9 . A method of screening a test compound and identifying the test compound as a drug suitable for the treatment of hyperglycemia comprising
 i) providing a test compound   ii) determining the ability of said test compound to inhibit the expression or activity of Gfi1; and   iii) identifying the test compound as a drug suitable for the treatment of hyperglycemia when the test compound inhibits the expression or activity of Gfi1.