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Diabetes Publish Ahead of Print published online ahead of print March 14, 2007
DOI: 10.2337/db06-1286
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Original Research

The STAT5A mediated induction of PDK4 expression by prolactin or growth hormone in adipocytes

Ursula A. White1, Ann A. Coulter1, Tiffany K. Miles1, and Jacqueline M. Stephens1

1Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803

Correspondence: jsteph1{at}lsu.edu

Key Words: adipocyte • prolactin • STAT5 • PDC • PDK

Objective.: The purpose of this study was to determine if PDK4 was expressed in adipocytes and if PDK4 expression was hormonally regulated in fat cells.

Research Design and Methods.: Both Northern blot and Western blot analyses were conducted on samples isolated from 3T3-L1 adipocytes following various treatments with prolactin, growth hormone, and/or insulin. Transfection of PDK4 promoter reporter constructs was performed. In addition, glucose uptake measurements were conducted.

Results.: Our studies demonstrate that prolactin and porcine growth hormone can induce the expression of PDK4 in 3T3-L1 adipocytes. Our studies also show that insulin pretreatment can attenuate the ability of these hormones to induce PDK4 mRNA expression. In addition, we identified a hormone responsive region in the murine PDK4 promoter and characterized a STAT5 binding site in this region which mediates the prolactin (sheep) and growth hormone (porcine) induction in PDK4 expression in 3T3-L1 adipocytes.

Conclusions.: PDK4 is a STAT 5A target gene. Prolactin is a potent inducer of PDK4 protein levels, results in an inhibition of insulin-stimulated glucose transport in fat cells, and likely contributes to prolactin induced insulin resistance.


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