Location: Children's Nutrition Research CenterTitle: A human virus improves diabetes) Author
Submitted to: Obesity
Publication Type: Abstract only
Publication Acceptance Date: 6/1/2010
Publication Date: 11/1/2010
Citation: Krishnapuram, R., Dhurandhar, E.J., Dubuisson, O., Kirk-Ballard, H., Bajpeyi, S., Butte, N.F., Johnson, W., McGlone, M., Reinhart, G., Rankinen, T., Bouchard, C., Cefalu, W.T., Ye, J., Javier, R., Zuberi, A., Dhurandhar, N.V. 2010. A human virus improves diabetes. Obesity. 18(2):S212. Interpretive Summary:
Technical Abstract: A single inoculation of mice with Ad36, a human adenovirus, lastingly improved high fat diet-induced-diabetes (DID), while Ad2, another human adenovirus did not. The study objective in these 2 studies was to determine if Ad36 could be used as a tool to reveal novel pathways for improving dysglycemia in humans. Study 1: To understand the mechanism, we compared protein or mRNA abundance of over 60 proteins obtained from adipose tissue, skeletal muscle and livers of DID mice, that were infected with Ad36, Ad2, or Mock infected 20-wk earlier. Based on our results, we postulate the following working model for the anti-diabetic action of Ad36 in mice. Ad36 upregulates glucose uptake in skeletal muscle and adipose tissue, via insulin-independent, but Ras-dependent, and phosphatidyl-inositol 3-kinase mediated upregulation of Glut4 and Glut1 transporters. In the liver, Ad36 reduces Glut2-mediated glucose output, increases glycogen, and reduces lipid storage. Furthermore, Ad36 robustly increases adiponectin, which improves glycemic control via AMP-activated protein kinase activation in skeletal muscle and liver. Collectively, this improves dysglycemia in mice. Study 2: We tested if humans, who were naturally infected with Ad36, have a better glycemic profile. Remarkably, natural Ad36 infection was associated with significantly better insulin sensitivity adjusted for age, sex, race, and adiposity, both, in adults and children. Considering that insulin signaling is often impaired in obesity or diabetes, the insulin-signaling independent glucose disposal by Ad36 may provide a particularly useful template for developing novel anti-diabetic drug targets, of relevance to humans.