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: db06-0299v1 56/6/1638    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 del Rincon, J.-P. Articles by O, M. Search for Related Content PubMed PubMed Citation Articles by del Rincon, J.-P. Articles by O, M. Social Bookmarking                What's this?

Growth Hormone Regulation of p85 Expression and Phosphoinositide 3-Kinase Activity in Adipose Tissue: Mechanism for Growth Hormone-Mediated Insulin Resistance

¹Department of Internal Medicine, University of Virginia, Charlottesville, VA
²Department of Pediatrics, University of Colorado Health Sciences Center
³Research Service, Denver VA Medical Center, Denver, CO
⁴Department of Medicine, University of Colorado Health Sciences Center
⁵Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center
⁶Edison Biotechnology Institute and the Department of Biomedical Sciences, Ohio University, Athens, OH

Correspondence: mot{at}virginia.edu

Phosphoinositide 3-kinase (PI3K) is involved in insulin-mediated effects on glucose uptake, lipid deposition and adiponectin secretion from adipocytes. Genetic disruption of the p85 regulatory subunit of PI3K increases insulin sensitivity, while elevated p85 levels are associated with insulin resistance through PI3K dependent and independent mechanisms. Adipose tissue plays a critical role in the antagonistic effects of growth hormone (GH) on insulin actions on carbohydrate and lipid metabolism through changes in gene transcription. Objective: Assess the role of the p85 subunit of PI3K and PI3K signaling in GH-mediated insulin resistance in adipose tissue. Research Design and Methods: p85 mRNA and protein expression and IRS-1-associated PI3K activity were measured in white adipose tissue (WAT) of mice with GH excess, deficiency and sufficiency. Additional studies using 3T3-F442A cells were conducted to confirm direct effects of GH on free p85 protein abundance. Results: p85 expression: 1) is decreased in WAT from mice with isolated GH deficiency; 2) is increased in WAT from mice with chronic GH excess; 3) is acutely up-regulated in WAT from GH-deficient and GH-sufficient mice following GH administration; 4) is directly up-regulated by GH in 3T3-F442A adipocytes. The insulin-induced increase in PI3K activity was robust in mice with GH-deficiency, but not in mice with GH excess. Conclusions: GH regulates p85 expression and PI3K activity in WAT and provides a potential explanation for: a) the insulin hypersensitivity and associated obesity and hyperadiponectinemia of GH-deficient mice; and b) the insulin resistance and associated reduced fat mass and hypoadiponectinemia of mice with GH excess.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				R P Rhoads, J W Kim, M E Van Amburgh, R A Ehrhardt, S J Frank, and Y R Boisclair Effect of nutrition on the GH responsiveness of liver and adipose tissue in dairy cows J. Endocrinol., October 1, 2007; 195(1): 49 - 58. [Abstract] [Full Text] [PDF]