Potential role of E4orf1 protein in aging-associated impairment in glycemic control

Aging constitutes a major risk factor for the development of type-2 diabetes (T2D) where glucose tolerance declines with age, resulting in a high prevalence of T2D and impaired glucose tolerance in the elderly population. Currently more than half of the 20 million U.S. adults with T2D are above the age of 60, and the largest increase in T2D prevalence is expected in the elderly. Obesity is a causative factor for T2D associated insulin resistance and hyperglycemia. Furthermore, the aging process is accelerated by hyperglycemia and effective treatment options are limited for the vulnerable aging population. One of the mechanisms contributing to aging associated hyperglycemia is resistance to insulin-mediated glucose disposal. Chronic hyperglycemia also accelerates aging by increasing pro-inflammatory milieu leading to impaired immune function. Although currently available anti-diabetic agents improve glycemic control, they have potential serious side effects in some cases. Therefore, additional and better drugs are urgently needed for treatment of insulin resistance and aging associated health risk factors. This review presents the novel use of a microbial protein, E4orf1 as a potential anti-diabetic agent, which functions independent of insulin and obesity, highlighting the role of unique sources for future drug development.