title: Insulin sparing action of adenovirus 36 and its E4orf1 protein.
abstract: Additional drugs are required to effectively manage diabetes and its complications. Recent studies have revealed protective effects of Ad36, a human adenovirus, and its E4orf1 protein on glucose disposal, which may be creatively harnessed to develop novel anti-diabetic agents. Experimental Ad36 infection improves hyperglycemia in animal models and natural Ad36 infection in humans is associated with better glycemic control. Available data indicate distinctive advantages for a drug that may mimic the action of Ad36/E4orf1. The key features of such a potential drug include the ability to increase glucose uptake by adipose tissue and skeletal muscle, to reduce hepatic glucose output independent of proximal insulin signaling, and to up-regulate adiponectin and its hepatic action. The effect of Ad36/E4orf1 on hepatocyte metabolism suggests a role for treating hepatic steatosis. Despite these potential advantages, considerable research is required before such a drug is developed. The in vivo efficacy and safety of E4orf1 in improving hyperglycemia remain unknown, and an appropriate drug delivery system is required. Nonetheless, Ad36 E4orf1 offers a research opportunity to develop a new anti-diabetic agent with multiple potential advantages and conceptually advances the use of a rather unconventional source, microbial proteins, for anti-diabetic drug development.
authors.affiliation: Infections and Obesity laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA. Nikhil.Dhurandhar@PBRC.EDU
authors.forename: Nikhil V
authors.initials: NV
authors.lastname: Dhurandhar
mesh_terms: D000256:Adenoviridae / Q000378:metabolism*; D000257:Adenoviridae Infections / Q000150:complications / Q000821:virology; D000818:Animals; D048909:Diabetes Complications / Q000821:virology; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000821:virology; D015195:Drug Design; D016903:Drug Monitoring; D004357:Drug Synergism; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D009856:Oncogene Proteins, Viral / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: C101120:E4 protein, Adenovirus 9; D007004:Hypoglycemic Agents; D007328:Insulin; D009856:Oncogene Proteins, Viral