HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) All Versions of this Article: db07-1313v1 57/7/1805    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, Z. Q Articles by Dhurandhar, N. V. Search for Related Content PubMed PubMed Citation Articles by Wang, Z. Q Articles by Dhurandhar, N. V. Social Bookmarking                What's this?

Human adenovirus type 36 enhances glucose uptake in diabetic and non-diabetic human skeletal muscle cells independent of insulin signaling

¹Division of Nutrition and Chronic Diseases
²Infections and Obesity Laboratory Pennington Biomedical Research Center, LSU system. Baton Rouge, LA 70808

Objective: Human adenovirus type 36 (Ad-36) increases adiposity, but improves insulin sensitivity in experimentally infected animals. We determined the ability of Ad-36 to increase glucose uptake by human skeletal muscle cells.

Research Design and Methods: The effect of Ad-36 on glucose uptake and cell signaling was determined in human primary skeletal muscle (HSKM) cells obtained from type 2 diabetic and healthy lean subjects. Ad-2, another human adenovirus, was used as a negative control. Gene expression and proteins of GLUT1 and GLUT4 were measured by real time PCR and Western Blotting. Role of Insulin and Ras signaling pathways was determined in Ad-36 infected HSKM cells.

Results: Ad-36 and Ad-2 infections were confirmed by the presence of respective viral mRNA and protein expressions. In a dose dependent manner, Ad-36 significantly increased glucose uptake in diabetic and non-diabetic HSKM cells. Ad-36 increased gene expression and protein abundance of GLUT1 and GLUT4, GLUT4 translocation to plasma membrane, and phosphotidyl inositol-3-kinase (PI3K) activity, in an insulin independent manner. In fact, Ad-36 decreased IRS-1 tyrosine phosphorylation, and IRS-1 and IRS-2 associated PI3K activities. On the other hand, Ad-36 increased Ras gene expression and protein abundance, and Ras RNAi abrogated Ad-36 induced PI3K activation, GLUT4 protein abundance and glucose uptake. These effects were not observed with Ad-2 infection.

Conclusion: Ad-36 infection increases glucose uptake in HSKM cells via Ras activated PI3K pathway, in an insulin independent manner. These findings may provide impetus to exploit the role of Ad-36 proteins as novel therapeutic targets for improving glucose handling.

Key Words: Infectobesity • insulin resistance • adipose tissue • metabolic remodeling • glucose uptake • Ad-36

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. M. Rogers, N. Mashtalir, M. A. Rathod, O. Dubuisson, Z. Wang, K. Dasuri, S. Babin, A. Gupta, N. Markward, W. T. Cefalu, et al. Metabolically Favorable Remodeling of Human Adipose Tissue by Human Adenovirus Type 36 Diabetes, September 1, 2008; 57(9): 2321 - 2331. [Abstract] [Full Text] [PDF]