Location: Location not imported yet.Title: Template to improve glycemic control without reducing adiposity or dietary fat) Author
Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/21/2011
Publication Date: 1/25/2011
Citation: Krishnapuram, R., Dhurandhar, E.J., Dubuisson, O., Kirk-Ballard, H., Bajpeyi, S., Butte, N., Sothern, M.S., Dhurandhar, N.V. 2011. Template to improve glycemic control without reducing adiposity or dietary fat. American Journal of Physiology - Endocrinology and Metabolism. 300:E779-E789. Interpretive Summary: Recent insights from animal and epidemiology studies suggest that the gut microbiota might be involved in the development of metabolic disorders such as diabetes and fatty liver disease. In this study, the investigators provide evidence that infecting mice with Ad36, a human adenovirus which is a group of viruses that infect the membranes (tissue linings) of the respiratory tract, the eyes, the intestines, and the urinary tract; improved blood glucose levels and decreased the amount of fat in the liver. Blood samples of adults and children were screened for Ad36 antibodies as an indicator of past natural infection. Ad36 infection was associated with lower blood glucose levels and fat in the liver. This study supports a role of the gut microbiota in the risk for metabolic disorders.
Technical Abstract: Drugs that improve chronic hyperglycemia independently of insulin signaling or reduction of adiposity or dietary fat intake may be highly desirable. Ad36, a human adenovirus, promotes glucose uptake in vitro independently of adiposity or proximal insulin signaling. We tested the ability of Ad36 to improve glycemic control in vivo and determined if the natural Ad36 infection in humans is associated with better glycemic control. C57BL/6J mice fed a chow diet or made diabetic with a high-fat (HF) diet were mock infected or infected with Ad36 or adenovirus Ad2 as a control for infection. Postinfection (pi), systemic glycemic control, hepatic lipid content, and cell signaling in tissues pertinent to glucose metabolism were determined. Next, sera of 1,507 adults and children were screened for Ad36 antibodies as an indicator of past natural infection. In chow-fed mice, Ad36 significantly improved glycemic control for 12 wk pi. In HF-fed mice, Ad36 improved glycemic control and hepatic steatosis up to 20 wk pi. In adipose tissue (AT), skeletal muscle (SM), and liver, Ad36 upregulated distal insulin signaling without recruiting the proximal insulin signaling. Cell signaling suggested that Ad36 increases AT and SM glucose uptake and reduces hepatic glucose release. In humans, Ad36 infection predicted better glycemic control and lower hepatic lipid content independently of age, sex, or adiposity. We conclude that Ad36 offers a novel tool to understand the pathways to improve hyperglycemia and hepatic steatosis independently of proximal insulin signaling, and despite a HF diet. This metabolic engineering by Ad36 appears relevant to humans for developing more practical and effective antidiabetic approaches.