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Science 5 December 2003: Vol. 302. no. 5651, pp. 1710 - 1711 DOI: 10.1126/science.1092952
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Insulin Signaling in Health and Disease
Morris F. White*
The signaling pathways used by insulin have been identified [M. White, Insulin Signaling Pathway, Sci. STKE (Connections Map, as seen November 2003), http://stke.sciencemag.org/cgi/cm/cmp_12069]. Now our challenge is to understand how the failure of these signals is associated with obesity and the progressive failure of pancreatic beta cells that leads to diabetes. Whether better management of chronic inflammation can improve insulin action is an important area of investigation. Drugs that stimulate IRS2 (insulin receptor substrate protein 2) synthesis or signaling might be a good starting point. This knowledge will lead to rational strategies that prevent or cure diabetes.
Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA.
* To whom correspondence should be addressed. E-mail: morris.white{at}joslin.harvard.edu
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The editors suggest the following Related Resources on Science sites:
In Science Signaling
- DATABASE OF CELL SIGNALING
Insulin Signaling Pathway
- Morris F. White
Sci. Signal. (Connections Map Pathway), http://stke.sciencemag.org/cgi/cm/stkecm;CMP_12069
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| PDF »
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| Full Text »
| PDF »
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| Abstract »
| Full Text »
| PDF »
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J. Biol. Chem.
280, 39723-39731
| Abstract »
| Full Text »
| PDF »
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- J. A. Kushner, L. Simpson, L. M. Wartschow, S. Guo, M. M. Rankin, R. Parsons, and M. F. White (2005)
J. Biol. Chem.
280, 39388-39393
| Abstract »
| Full Text »
| PDF »
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| Abstract »
| PDF »
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- M. Luo, S. Reyna, L. Wang, Z. Yi, C. Carroll, L. Q. Dong, P. Langlais, S. T. Weintraub, and L. J. Mandarino (2005)
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146, 4410-4416
| Abstract »
| Full Text »
| PDF »
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Mol. Biol. Cell
16, 4454-4461
| Abstract »
| Full Text »
| PDF »
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| Abstract »
| Full Text »
| PDF »
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- F. G. Haj, J. M. Zabolotny, Y.-B. Kim, B. B. Kahn, and B. G. Neel (2005)
J. Biol. Chem.
280, 15038-15046
| Abstract »
| Full Text »
| PDF »
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- S. Y. Park, G. H. Choi, H. I. Choi, J. Ryu, C. Y. Jung, and W. Lee (2005)
J. Biol. Chem.
280, 9855-9864
| Abstract »
| Full Text »
| PDF »
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- X. Yi, M. Schubert, N. S. Peachey, K. Suzuma, D. J. Burks, J. A. Kushner, I. Suzuma, C. Cahill, C. L. Flint, M. A. Dow, et al. (2005)
J. Neurosci.
25, 1240-1248
| Abstract »
| Full Text »
| PDF »
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- M. W. Schwartz and D. Porte Jr. (2005)
Science
307, 375-379
| Abstract »
| Full Text »
| PDF »
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- Y. Li, T. J. Soos, X. Li, J. Wu, M. DeGennaro, X. Sun, D. R. Littman, M. J. Birnbaum, and R. D. Polakiewicz (2004)
J. Biol. Chem.
279, 45304-45307
| Abstract »
| Full Text »
| PDF »
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- M. Cully, A. Elia, S.-H. Ong, V. Stambolic, T. Pawson, M.-S. Tsao, and T. W. Mak (2004)
PNAS
101, 15358-15363
| Abstract »
| Full Text »
| PDF »
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Brain
127, 2193-2200
| Abstract »
| Full Text »
| PDF »
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- D. B. Coursin and R. C. Prielipp (2004)
Anesth. Analg.
99, 316-318
| Full Text »
| PDF »
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- M. L. Slattery, W. Samowitz, K. Curtin, K. N. Ma, M. Hoffman, B. Caan, and S. Neuhausen (2004)
Cancer Epidemiol. Biomarkers Prev.
13, 1206-1214
| Abstract »
| Full Text »
| PDF »
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- V. Brussee, F. A. Cunningham, and D. W. Zochodne (2004)
Diabetes
53, 1824-1830
| Abstract »
| Full Text »
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- S. R. Broussard, R. H. McCusker, J. E. Novakofski, K. Strle, W. H. Shen, R. W. Johnson, R. Dantzer, and K. W. Kelley (2004)
J. Immunol.
172, 7713-7720
| Abstract »
| Full Text »
| PDF »
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