Gillian Air  /  Sanjay Bidichandani  /  Robert Broyles
  Paul DeAngelis  /  Jay Hanas  /  Martin Levine  /  Guangpu Li 

Jialing Lin  /  Hiroyuki Matsumoto  / Blaine Mooers /  Ann Louise Olson 

Karla Rodgers  /  Robert Steinberg  /  Leon Unger  /  Paul Weigel   /  Christopher West 

Transcriptional regulation of the insulin-regulated facilitative glucose transporter (GLUT4) gene; mechanisms of insulin-mediated GLUT4 translocation.

The major physiologic action of insulin is to increase glucose uptake and storage in adipose tissue, skeletal muscle and heart.  This accomplished largely through the recruitment of a specialized facilitative glucose transport protein to the cell surface under insulin action.  This glucose transport protein (GLUT4) is an integral membrane protein.  Under basal conditions, when plasma insulin levels are low, GLUT4 resides in a small, intracellular vesicle in muscle and adipose tissues.  When insulin activates its cell surface receptor, a signal is generated which results in the stimulation of exocytosis of the intracellular GLUT4-vesicles to the plasma membrane (see Figure below).  This, in turn, facilitates the uptake of glucose into the cells. 

In addition to GLUT4 translocation, the size of the cellular pool of GLUT4 has a profound effect on insulin sensitivity.  GLUT4 protein levels are regulated at the transcriptional level in a variety of normal and pathophysiologic states.

Insulin resistant glucose transport in muscle and adipose tissue results from both defects in the ability of the insulin-signaling pathway to stimulate the recruitment of GLUT4 to the plasma membrane and a decrease in the total pool of GLUT4 protein. 

Our laboratory has had a long-standing interest in the molecular processes that regulate insulin-mediated exocytosis of GLUT4 vesicles as well as the transcriptional regulation of the GLUT4 gene. Using transgenic mice, we have begun to understand the molecular basis that underlies the transcriptional regulation of the GLUT4 gene in complex physiologic states.  Understanding these areas of GLUT4 cellular and molecular biology are crucial to understanding the development of diabetes.

Selected Publications:                                                     [Search Pubmed]

Ann Louise Olson, Craig A. Eyster, Quwanza S. Duggins, John B. Knight:  Insulin promotes microtubule polymerization by a of phosphatidylinositol 3-kinase independent, actin dependent pathway in 3T3-L1 adipocytes, Endocrinology, 144:5030-5039, 2003.

John B. Knight, Craig A. Eyster, Beth A. Griesel, Ann Louise Olson: Regulation of the Human GLUT4 Promoter: Interaction Between a Novel Transcriptional Activator (GEF) and MEF2A, Proc. Natl. Acad. Sci. 100:14725-14730, 2003

Craig A. Eyster, Quwanza S. Duggins, Ann Louise Olson Expression of a constitutively active Akt/PKB signals GLUT4 translocation in the absence of an intact actin cytoskeleton.  J. Biol. Chem. 280:17978-17985, 2005.

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