title: Positive and negative regulation of glucose uptake by hyperosmotic stress.
abstract: This review will provide insight on the current understanding of the intracellular signaling mechanisms by which hyperosmolarity mimics insulin responses such as Glut 4 translocation and glucose transport but also antagonizes insulin effects. Glucose uptake induced by insulin is largely dependent on the PI 3-kinase/PKB pathway. In both adipocyte and muscle cells, hyperosmolarity promotes glucose uptake by multiple mechanisms which do not require PI 3-kinase/PKB pathway but are dependent on the cell type. In muscle, osmotic stress induces glucose uptake by stimulation of AMP-Kinase and/or inhibition of Glut 4 endocytosis. In adipocytes, activation of Gab1-dependent signaling pathway plays an important role in osmotic stress-mediated glucose uptake. Apart of its insulin-like effects, hyperosmolarity can lead to cellular insulin resistance mediated by both prevention of PKB activation and inhibition of the Insulin Receptor Substrate-1 (IRS1) function. Serine phosphorylation and degradation of IRS1 negatively regulate its functions. Understanding how osmotic stress induces glucose transport or mediates insulin resistance may provide novel targets for strategies to enhance glucose transport or to prevent insulin resistance.
authors.affiliation: INSERM U 568 and IFR 50, Faculté de Médecine, Avenue de Valombrose, 06107 Nice Cedex 02, France. gual@unice.fr
authors.forename: P
authors.initials: P
authors.lastname: Gual
authors.forename: Y
authors.initials: Y
authors.lastname: Le Marchand-Brustel
authors.forename: Jf
authors.initials: J
authors.lastname: Tanti
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D001692:Biological Transport; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D006982:Hypertonic Solutions; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D032342:Muscle Cells / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009997:Osmotic Pressure; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D006982:Hypertonic Solutions; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D005947:Glucose