Insulin sparing action of Adenovirus 36 and its E4orf1 protein

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. (C) 2013 Elsevier Inc. All rights reserved.