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Sci. STKE, 25 January 2005
Vol. 2005, Issue 268, p. pe4
[DOI: 10.1126/stke.2682005pe4]
PERSPECTIVES
Ser/Thr Phosphorylation of IRS Proteins: A Molecular Basis for Insulin Resistance
Yehiel Zick*
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Summary:
S6K1, like other serine and threonine kinases activated by insulin (such as mTOR and PKC), has recently been shown to participate in negative feedback mechanisms aimed at terminating insulin signaling through IRS (insulin receptor substrate) phosphorylation. Such homeostatic mechanisms can also be activated by excess nutrients or inducers of insulin resistance (such as fatty acids and proinflammatory cytokines) to produce an insulin-resistant state that often leads to the development of diabetes. Identification of the specific kinases involved in such insulin resistance pathways can help lead to the rational design of novel therapeutic agents for treating insulin resistance and type 2 diabetes.
N. S. Kalupahana, K. J. Claycombe, and N. Moustaid-Moussa (2011)
Adv Nutr
2, 304-316
|PDF »
Chronically Increased S6K1 Is Associated with Impaired IRS1 Signaling in Skeletal Muscle of GDM Women with Impaired Glucose Tolerance Postpartum.
L. A. Barbour, C. E. McCurdy, T. L. Hernandez, and J. E. Friedman (2011)
J. Clin. Endocrinol. Metab.
96, 1431-1441
|Abstract »|Full Text »|PDF »
The Double-stranded RNA-dependent Protein Kinase Differentially Regulates Insulin Receptor Substrates 1 and 2 in HepG2 Cells.
X. Yang, A. Nath, M. J. Opperman, and C. Chan (2010)
Mol. Biol. Cell
21, 3449-3458
|Abstract »|Full Text »|PDF »
Elimination of Negative Feedback Control Mechanisms Along the Insulin Signaling Pathway Improves {beta}-Cell Function Under Stress.
D. Gurevitch, S. Boura-Halfon, R. Isaac, G. Shahaf, M. Alberstein, D. Ronen, E. C. Lewis, and Y. Zick (2010)
Diabetes
59, 2188-2197
|Abstract »|Full Text »|PDF »
Lipoic acid increases heat shock protein expression and inhibits stress kinase activation to improve insulin signaling in skeletal muscle from high-fat-fed rats.
A. A. Gupte, G. L. Bomhoff, J. K. Morris, B. K. Gorres, and P. C. Geiger (2009)
J Appl Physiol
106, 1425-1434
|Abstract »|Full Text »|PDF »
Insulin signalling in the heart.
L. Bertrand, S. Horman, C. Beauloye, and J.-L. Vanoverschelde (2008)
Cardiovasc Res
79, 238-248
|Abstract »|Full Text »|PDF »
Protein Kinase C Function in Muscle, Liver, and {beta}-Cells and Its Therapeutic Implications for Type 2 Diabetes.
C. Schmitz-Peiffer and T. J. Biden (2008)
Diabetes
57, 1774-1783
|Full Text »|PDF »
Mammalian target of rapamycin inhibition as a therapeutic strategy in the management of urologic malignancies.
Negative feedback regulation of Rac in leukocytes from mice expressing a constitutively active phosphatidylinositol 3-kinase {gamma}.
C. Costa, L. Barberis, C. Ambrogio, A. D. Manazza, E. Patrucco, O. Azzolino, P. O. Neilsen, E. Ciraolo, F. Altruda, G. D. Prestwich, et al. (2007)
PNAS
104, 14354-14359
|Abstract »|Full Text »|PDF »
), has recently been shown to participate in negative feedback mechanisms aimed at terminating insulin signaling through IRS (insulin receptor substrate) phosphorylation. Such homeostatic mechanisms can also be activated by excess nutrients or inducers of insulin resistance (such as fatty acids and proinflammatory cytokines) to produce an insulin-resistant state that often leads to the development of diabetes. Identification of the specific kinases involved in such insulin resistance pathways can help lead to the rational design of novel therapeutic agents for treating insulin resistance and type 2 diabetes.
