Methods and reagents for treating diabetes

Abstract

Disclosed are methods for treating or limiting development of diabetes, by transplanting into the eye of a subject with diabetes or at risk of diabetes an amount effective to treat or limit development of diabetes of insulin-producing cells engineered to reduce expression of a β3 subunit of Cav (Cavβ3).

I claim: 
     
         1 . A method for treating or limiting development of diabetes, comprising transplanting into the eye of a subject with diabetes or at risk of diabetes an amount effective to treat or limit development of diabetes of insulin-producing cells engineered to reduce expression of a β3 subunit of Cav (Cavβ3). 
     
     
         2 . The method of  claim 1 , wherein the insulin-producing cells are engineered to disrupt each copy of the Cavβ3 gene. 
     
     
         3 . The method of  claim 1 , wherein the insulin-producing cells are engineered to reduce expression of apoCIII. 
     
     
         4 . The method of  claim 3 , wherein the insulin-producing cells are engineered to disrupt each copy of the apoCIII gene. 
     
     
         5 . The method of  claim 1 , wherein the insulin-producing cells are engineered to reduce expression of one or more chemokines, including but not limited to CCL2, CCL3, CCL5, CXCL1, CXCL9, CXCL10, and/or CXCL11, and/or one or more cytokines including but not limited to IL-6 and/or IL-8. 
     
     
         6 . The method of  claim 5 , wherein the insulin-producing cells are engineered to disrupt each copy of the one or more chemokine genes and/or the one or more cytokine genes. 
     
     
         7 . The method of  claim 1 , wherein the insulin-producing cells are engineered to reduce expression of one or more major histocompatibility complex (MHC) class I proteins. 
     
     
         8 . The method of  claim 7 , wherein the insulin-producing cells are engineered to disrupt each copy of the one or more MHC class I proteins. 
     
     
         9 . The method of  claim 1 , wherein the insulin-producing cells are engineered to increase expression of one or more proteins beneficial to insulin producing cells, including but not limited to GLP1 receptors, insulin receptors, and/or cytokine IL1B. 
     
     
         10 . The method of  claim 1 , wherein the insulin-producing cells comprise isolated pancreatic islets or isolated pancreatic β cells, such as isolated human pancreatic islets or isolated human pancreatic β cells. 
     
     
         11 . The method of  claim 1 , wherein the transplantation into the eye involves transplantation into the anterior chamber of the eye. 
     
     
         12 . The method of  claim 11 , wherein the transplantation into the anterior chamber of the eye involves injection through the cornea. 
     
     
         13 . The method of  claim 1 , wherein the subject, such as a human subject, has diabetes and the transplanting comprising transplanting into the eye of a subject with diabetes an amount effective to treat diabetes. 
     
     
         14 . The method of  claim 14 , wherein the subject has type 2 diabetes. 
     
     
         15 . The method of  claim 14 , wherein the subject has type 1 diabetes. 
     
     
         16 . The method of  claim 1 , wherein the subject, such as a human subject, is at risk of diabetes and the transplanting comprising transplanting into the eye of a subject at risk of diabetes an amount effective to limit development of diabetes. 
     
     
         17 . The method of  claim 16 , wherein the subject is at risk of type 2 diabetes. 
     
     
         18 . The method of  claim 16 , wherein the subject is at risk of type 1 diabetes. 
     
     
         19 . The method of  claim 1 , wherein the subject, such as a human subject, overexpresses Cavβ3 compared to a control. 
     
     
         20 . A recombinant cell comprising an insulin-producing cell engineered to reduce expression of a β3 subunit of Cav (Cavβ3).