Insulin sparing action of adenovirus 36 and its E4orf1 protein

J Diabetes Complications. Mar-Apr 2013;27(2):191-9. doi: 10.1016/j.jdiacomp.2012.09.006. Epub 2012 Dec 12.


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.

Publication types

  • Review

MeSH terms

  • Adenoviridae / metabolism*
  • Adenoviridae Infections / complications
  • Adenoviridae Infections / virology
  • Animals
  • Diabetes Complications / virology
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / virology
  • Drug Design
  • Drug Monitoring
  • Drug Synergism
  • Humans
  • Hyperglycemia / prevention & control*
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / therapeutic use
  • Insulin / administration & dosage*
  • Insulin / therapeutic use
  • Oncogene Proteins, Viral / metabolism*
  • Oncogene Proteins, Viral / therapeutic use


  • E4 protein, Adenovirus 9
  • Hypoglycemic Agents
  • Insulin
  • Oncogene Proteins, Viral