Adenovirus 36 E4 ORF 1 Gene and Protein and Their Uses

Abstract

Expression of the E4 orf 1 gene of Ad-36 alone has been discovered to be responsible for the increased insulin sensitivity observed in Ad-36 infected animals, including increased adipogenesis. Ad-36 E4 orf 1 protein can be used to increase insulin sensitivity and ameliorate diabetes. Additionally, drugs that mimic the action of Ad-36 E4 orf 1 protein could be found. Ad-36 E4 orf 1 could also be used to increase fat cells in lipodystrophy. We have also discovered that Ad-36 infection in human skeletal muscle cells increased differentiation and insulin independent glucose uptake. It is expected that infection with Ad-36 E4 orf 1 gene will also cause these effects.

1 - 22 . (canceled) 
     
     
         23 . An isolated analog or derivative of Ad-36 E4 orf 1 protein. 
     
     
         24 . The isolated analog or derivative of  claim 23 , wherein Ad-36 E4 orf 1 protein has the amino acid sequence of SEQ ID NO:2. 
     
     
         25 . The isolated analog or derivative of  claim 23 , wherein said analog or derivative has substantially similar structure as SEQ ID NO:2 and qualitatively similar activity as SEQ ID NO:2. 
     
     
         26 . The isolated analog or derivative of  claim 25 , wherein said activity is increasing a patient's insulin sensitivity following administration of a therapeutically effective amount of analog or derivative. 
     
     
         27 . The isolated analog or derivative of  claim 25 , wherein said activity is increasing the number of adipose tissue cells in a patient following administration of a therapeutically effective amount of analog or derivative. 
     
     
         28 . The isolated analog or derivative of  claim 25 , wherein said activity is decreasing the concentration of serum glucose in a diabetic patient following administration of a therapeutically effective amount of analog or derivative. 
     
     
         29 . A method of treating or ameliorating one or more symptoms of a disease in a mammalian patient wherein the disease is chosen from the group consisting of lipodystrophy, diabetes, and insulin resistance, said method comprising administering to the patient a therapeutically effective amount of an analog or derivative of Ad-36 E4 orf 1 protein, whose amino acid sequence comprises SEQ ID NO: 2, wherein the patient's symptoms improve following said administering. 
     
     
         30 . The method of  claim 29 , wherein the diseases is insulin resistance, and wherein the patient's insulin sensitivity increases following said administering. 
     
     
         31 . The method of  claim 29 , wherein the disease is lipodystrophy and wherein the number of adipose tissue cells in the patient increases following said administering. 
     
     
         32 . The method of  claim 29 , wherein the diseases is diabetes and the symptom is a high concentration of serum glucose, and wherein the concentration of serum glucose decreases following said administering. 
     
     
         33 . The method of  claim 29 , wherein a pharmaceutical composition comprising the analog or derivative, a pharmaceutical and a pharmaceutically acceptable carrier are administered to the patient. 
     
     
         34 . A pharmaceutical composition comprising the analog or derivative of  claim 23 , a pharmaceutical and a pharmaceutically acceptable carrier.