Adenovirus infection results in alterations of insulin signaling and glucose homeostasis

作者：Jiang Shaoning; Gavrikova Tatyana A; Pereboev Alexander; Messina Joseph L^*

来源：American Journal of Physiology - Endocrinology And Metabolism, 2010, 298(6): E1295-E1304.

DOI：10.1152/ajpendo.00723.2009

• liver
• insulin receptor
• insulin receptor substrates
• tumor necrosis factor-alpha
• Kupffer cells

Jiang S, Gavrikova TA, Pereboev A, Messina JL. Adenovirus infection results in alterations of insulin signaling and glucose homeostasis. Am J Physiol Endocrinol Metab 298: E1295-E1304, 2010. First published April 13, 2010; doi:10.1152/ajpendo.00723.2009.-Recombinant adenovirus (Ad) vectors can initiate an inflammatory response, limiting its use in gene therapy and basic research. Despite increased efforts to better understand Ad infection, little is known about how it affects cellular metabolic responses. In the current studies, we explored the effects of Ad vectors on insulin signaling molecules and glucose homeostasis. Nonreplicative Ad vectors were injected into rats through the tail vein, and at 4-13 days postinjection insulin signaling and glucose tolerance were examined. Ad vector infection significantly reduced total levels of the insulin receptor (IR), and insulin receptor substrates 1 and 2 (IRS-1, IRS-2) in the liver of rats, resulting in decreased insulin-induced tyrosine phosphorylation of IR, IRS-1, and IRS-2, and decreased interaction of IRS-1 and IRS-2 with phosphoinositide 3-kinase (PI3K). In addition, Ad infection resulted in impaired systemic glucose homeostasis, which recovered by 13 days, after the protein levels of IR, IRS-1, and IRS-2 had started to normalize. Expression of a TNF inhibitor or Kupffer cell depletion attenuated the Ad vector-induced decreases of insulin signaling molecules, indicating a potential role of Kupffer cell activation in this process. These studies provide evidence that systemic administration of Ad vectors can impair insulin signaling in liver, resulting in altered systemic glucose metabolism. Thus, effects of Ad vector infection on insulin action and glucose metabolism need to be considered when Ad vectors are used in research or gene therapy and may be more broadly applicable to other viral agents.

• 出版日期2010-6