Related Content
In Other Science Products(Separate subscription may be required)
Search Google Scholar for:
More Information
Related Jobs from ScienceCareers
|
|
Science 5 December 2003: Vol. 302. no. 5651, pp. 1710 - 1711 DOI: 10.1126/science.1092952
|
|
Viewpoints
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
Read the Full Text
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
| Canonical Pathway »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
- Starvation and Triglycerides Reverse the Obesity-Induced Impairment of Insulin Transport at the Blood-Brain Barrier.
- A. Urayama and W. A. Banks (2008)
Endocrinology
149, 3592-3597
| Abstract »
| Full Text »
| PDF »
- A high-carbohydrate diet in the immediate postnatal life of rats induces adaptations predisposing to adult-onset obesity.
- M. Srinivasan, P. Mitrani, G. Sadhanandan, C. Dodds, S. Shbeir-ElDika, S. Thamotharan, H. Ghanim, P. Dandona, S. U Devaskar, and M. S Patel (2008)
J. Endocrinol.
197, 565-574
| Abstract »
| Full Text »
| PDF »
- Insulin resistance induced by tumor necrosis factor-{alpha} in myocytes and brown adipocytes.
- M. Lorenzo, S. Fernandez-Veledo, R. Vila-Bedmar, L. Garcia-Guerra, C. De Alvaro, and I. Nieto-Vazquez (2008)
J Anim Sci
86, E94-E104
| Abstract »
| Full Text »
| PDF »
- Peripubertal Hyperinsulinemia Upregulates Phosphatidylinositol 3-Kinase/Akt Pathway in Rat Ovaries.
- S. Chakrabarty and M. Nagamani (2008)
Reproductive Sciences
15, 274-284
| Abstract »
| PDF »
- The Repression of IRS2 Gene by ATF3, a Stress-Inducible Gene, Contributes to Pancreatic {beta}-Cell Apoptosis.
- D. Li, X. Yin, E. J. Zmuda, C. C. Wolford, X. Dong, M. F. White, and T. Hai (2008)
Diabetes
57, 635-644
| Abstract »
| Full Text »
| PDF »
- Nuclear Exclusion of Forkhead Box O and Elk1 and Activation of Nuclear Factor-{kappa}B Are Required for C2C12-RasV12C40 Myoblast Differentiation.
- C. De Alvaro, I. Nieto-Vazquez, J. M. Rojas, and M. Lorenzo (2008)
Endocrinology
149, 793-801
| Abstract »
| Full Text »
| PDF »
- Insulin Receptor Substrate-1 Deficiency Promotes Apoptosis in the Putative Intestinal Crypt Stem Cell Region, Limits Apcmin/+ Tumors, and Regulates Sox9.
- N. M. Ramocki, H. R. Wilkins, S. T. Magness, J. G. Simmons, B. P. Scull, G. H. Lee, K. K. McNaughton, and P. K. Lund (2008)
Endocrinology
149, 261-267
| Abstract »
| Full Text »
| PDF »
- Insulin treatment enhances the myocardial angiogenic response in diabetes..
- M. Boodhwani, N. R. Sodha, S. Mieno, B. Ramlawi, S.-H. Xu, J. Feng, R. T. Clements, M. Ruel, and F. W. Sellke (2007)
J. Thorac. Cardiovasc. Surg.
134, 1453-1460
| Abstract »
| Full Text »
| PDF »
- Angiotensin-(1 7) stimulates the phosphorylation of JAK2, IRS-1 and Akt in rat heart in vivo: role of the AT1 and Mas receptors.
- J. F. Giani, M. M. Gironacci, M. C. Munoz, C. Pena, D. Turyn, and F. P. Dominici (2007)
Am J Physiol Heart Circ Physiol
293, H1154-H1163
| Abstract »
| Full Text »
| PDF »
- Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis.
- A. Taguchi, L. M. Wartschow, and M. F. White (2007)
Science
317, 369-372
| Abstract »
| Full Text »
| PDF »
- Molecular mechanism of bis(maltolato)oxovanadium(IV)-induced insulin signaling in 3T3-L1 and IM9 cells: impact of dexamethasone.
- S. Bose, M A. Farah, H.-C. Jung, J.-H. Lee, and Y. Kim (2007)
J. Mol. Endocrinol.
38, 627-649
| Abstract »
| Full Text »
| PDF »
- Global Assessment of Regulation of Phosphorylation of Insulin Receptor Substrate-1 by Insulin In Vivo in Human Muscle.
- Z. Yi, P. Langlais, E. A. De Filippis, M. Luo, C. R. Flynn, S. Schroeder, S. T. Weintraub, R. Mapes, and L. J. Mandarino (2007)
Diabetes
56, 1508-1516
| Abstract »
| Full Text »
| PDF »
- Skeletal muscle lipid deposition and insulin resistance: effect of dietary fatty acids and exercise.
- M. P Corcoran, S. Lamon-Fava, and R. A Fielding (2007)
Am. J. Clinical Nutrition
85, 662-677
| Abstract »
| Full Text »
| PDF »
- Protein-Tyrosine Phosphatase 1B-Deficient Myocytes Show Increased Insulin Sensitivity and Protection Against Tumor Necrosis Factor-{alpha}-Induced Insulin Resistance.
- I. Nieto-Vazquez, S. Fernandez-Veledo, C. de Alvaro, C. M. Rondinone, A. M. Valverde, and M. Lorenzo (2007)
Diabetes
56, 404-413
| Abstract »
| Full Text »
| PDF »
- Insulin potentiates TRPC3-mediated cation currents in normal but not in insulin-resistant mouse cardiomyocytes.
- J. Fauconnier, J. T. Lanner, A. Sultan, S.-J. Zhang, A. Katz, J. D. Bruton, and H. Westerblad (2007)
Cardiovasc Res
73, 376-385
| Abstract »
| Full Text »
| PDF »
- The Reciprocal Stability of FOXO1 and IRS2 Creates a Regulatory Circuit that Controls Insulin Signaling.
- S. Guo, S. L. Dunn, and M. F. White (2006)
Mol. Endocrinol.
20, 3389-3399
| Abstract »
| Full Text »
| PDF »
- Saturated fatty acids inhibit induction of insulin gene transcription by JNK-mediated phosphorylation of insulin-receptor substrates.
- G. Solinas, W. Naugler, F. Galimi, M.-S. Lee, and M. Karin (2006)
PNAS
103, 16454-16459
| Abstract »
| Full Text »
| PDF »
- Hybrid Receptors Formed by Insulin Receptor (IR) and Insulin-like Growth Factor I Receptor (IGF-IR) Have Low Insulin and High IGF-1 Affinity Irrespective of the IR Splice Variant.
- R. Slaaby, L. Schaffer, I. Lautrup-Larsen, A. S. Andersen, A. C. Shaw, I. S. Mathiasen, and J. Brandt (2006)
J. Biol. Chem.
281, 25869-25874
| Abstract »
| Full Text »
| PDF »
- PI3-kinase activity modulates apo B available for hepatic VLDL production in apobec-1-/- mice.
- D. V. Chirieac, N. O. Davidson, C. E. Sparks, and J. D. Sparks (2006)
Am J Physiol Gastrointest Liver Physiol
291, G382-G388
| Abstract »
| Full Text »
| PDF »
- Molecular Mechanisms of Insulin Resistance: Serine Phosphorylation of Insulin Receptor Substrate-1 and Increased Expression of p85{alpha}: The Two Sides of a Coin..
- B. Draznin (2006)
Diabetes
55, 2392-2397
| Abstract »
| Full Text »
| PDF »
- The role of Ca2+ influx for insulin-mediated glucose uptake in skeletal muscle..
- J. T. Lanner, A. Katz, P. Tavi, M. E. Sandstrom, S.-J. Zhang, C. Wretman, S. James, J. Fauconnier, J. Lannergren, J. D. Bruton, et al. (2006)
Diabetes
55, 2077-2083
| Abstract »
| Full Text »
| PDF »
- Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway.
- A. Yamamoto, M. L. Cremona, and J. E. Rothman (2006)
J. Cell Biol.
172, 719-731
| Abstract »
| Full Text »
| PDF »
- Exendin-4 Uses Irs2 Signaling to Mediate Pancreatic beta Cell Growth and Function.
- S. Park, X. Dong, T. L. Fisher, S. Dunn, A. K. Omer, G. Weir, and M. F. White (2006)
J. Biol. Chem.
281, 1159-1168
| Abstract »
| Full Text »
| PDF »
- Physiological and Pathological Changes in Glucose Regulate Brain Akt and Glycogen Synthase Kinase-3.
- B. Clodfelder-Miller, P. De Sarno, A. A. Zmijewska, L. Song, and R. S. Jope (2005)
J. Biol. Chem.
280, 39723-39731
| Abstract »
| Full Text »
| PDF »
- Hormonal Regulation of Male Reproductive Tract Development.
- S. VERMA-KURVARI, S. NEF, and L. F. PARADA (2005)
Ann. N.Y. Acad. Sci.
1061, 1-8
| Abstract »
| Full Text »
| PDF »
- Phosphatase and Tensin Homolog Regulation of Islet Growth and Glucose Homeostasis.
- 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 »
- An overview of the central control of weight regulation and the effect of antipsychotic medication.
- S. Tighe and T. Dinan (2005)
J Psychopharmacol
19, 36-46
| Abstract »
| PDF »
- Identification of Insulin Receptor Substrate 1 Serine/Threonine Phosphorylation Sites Using Mass Spectrometry Analysis: Regulatory Role of Serine 1223.
- M. Luo, S. Reyna, L. Wang, Z. Yi, C. Carroll, L. Q. Dong, P. Langlais, S. T. Weintraub, and L. J. Mandarino (2005)
Endocrinology
146, 4410-4416
| Abstract »
| Full Text »
| PDF »
- Sprouty-2 Overexpression in C2C12 Cells Confers Myogenic Differentiation Properties in the Presence of FGF2.
- C. de Alvaro, N. Martinez, J. M. Rojas, and M. Lorenzo (2005)
Mol. Biol. Cell
16, 4454-4461
| Abstract »
| Full Text »
| PDF »
- Insulin and Inositol 1,4,5-Trisphosphate Trigger Abnormal Cytosolic Ca2+ Transients and Reveal Mitochondrial Ca2+ Handling Defects in Cardiomyocytes of ob/ob Mice.
- J. Fauconnier, J. T. Lanner, S.-J. Zhang, P. Tavi, J. D. Bruton, A. Katz, and H. Westerblad (2005)
Diabetes
54, 2375-2381
| Abstract »
| Full Text »
| PDF »
- Liver-specific Protein-tyrosine Phosphatase 1B (PTP1B) Re-expression Alters Glucose Homeostasis of PTP1B-/-Mice.
- 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 »
- Depletion of Mitochondrial DNA Causes Impaired Glucose Utilization and Insulin Resistance in L6 GLUT4myc Myocytes.
- 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 »
- Insulin Receptor Substrate 2 Is Essential for Maturation and Survival of Photoreceptor Cells.
- 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 »
- Diabetes, Obesity, and the Brain.
- M. W. Schwartz and D. Porte Jr. (2005)
Science
307, 375-379
| Abstract »
| Full Text »
| PDF »
- Protein Kinase C {theta} Inhibits Insulin Signaling by Phosphorylating IRS1 at Ser1101.
- 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 »
- grb2 heterozygosity rescues embryonic lethality but not tumorigenesis in pten+/- mice.
- 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 »
- Accelerated diabetic neuropathy in axons without neurofilaments.
- D. W. Zochodne, H.-S. Sun, C. Cheng, and J. Eyer (2004)
Brain
127, 2193-2200
| Abstract »
| Full Text »
| PDF »
- The New Anesthesia Diet Plan: Keeping Perioperative Carbs in Check.
- D. B. Coursin and R. C. Prielipp (2004)
Anesth. Analg.
99, 316-318
| Full Text »
| PDF »
- Associations among IRS1, IRS2, IGF1, and IGFBP3 Genetic Polymorphisms and Colorectal Cancer.
- 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 »
- Direct Insulin Signaling of Neurons Reverses Diabetic Neuropathy.
- V. Brussee, F. A. Cunningham, and D. W. Zochodne (2004)
Diabetes
53, 1824-1830
| Abstract »
| Full Text »
| PDF »
- IL-1{beta} Impairs Insulin-Like Growth Factor I-Induced Differentiation and Downstream Activation Signals of the Insulin-Like Growth Factor I Receptor in Myoblasts.
- 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 »
|
|