The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism
Open accessAbstract
Hepatic insulin resistance is a critical component in the development of type 2 diabetes mellitus. In many cases, insulin resistance in liver is associated with reduced expression of both major insulin receptor substrate (IRS) proteins, IRS-1 and IRS-2. To investigate the specific functions of IRS-1 and IRS-2 in regulating liver function in vivo, we developed an adenovirus-mediated RNA interference technique in which short hairpin RNAs (shRNAs) are used to knock down IRS-1, IRS-2, or both, by 70-80% in livers of WT mice. The knockdown of IRS-1 resulted in an upregulation of the gluconeogenic enzymes glucose-6 phosphatase and phosphoenolpyruvate carboxykinase, as well as a marked increase in hepatic nuclear factor-4 alpha. Decreased IRS-1 was also associated with a decrease in glucokinase expression and a trend toward increased blood glucose, whereas knockdown of IRS-2 resulted in the upregulation of lipogenic enzymes SREBP-1c and fatty acid synthase, as well as increased hepatic lipid accumulation. The concomitant injection of IRS-1 and IRS-2 adenoviral shRNAs resulted in systemic insulin resistance, glucose intolerance, and hepatic steatosis. The alterations in the dual-knockdown mice were associated with defective Akt activation and Foxo1 phosphorylation. Taken together, our results demonstrate that hepatic IRS-1 and IRS-2 have complementary roles in the control of hepatic metabolism, with IRS-1 more closely linked to glucose homeostasis and IRS-2 more closely linked to lipid metabolism.
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Cites
Rational siRNA design for RNA interference
Reynolds, A., Leake, D., Boese, Q., Scaringe, S., Marshall, W. S., & Khvorova, A. (2004) · Nature Biotechnology · doi:10.1038/nbt936 · Cited by 2,094
Insulin-regulated hepatic gluconeogenesis through FOXO1–PGC-1α interaction
Puigserver, P., Rhee, J., Donovan, J., Walkey, C. J., Yoon, J. C., Oriente, F., Kitamura, Y., Altomonte, J., Dong, H., Accili, D., et al. (2003) · Nature · doi:10.1038/nature01667 · Cited by 1,487
Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene
Araki, E., Lipes, M. A., Patti, M.-E., Brüning, J. C., Haag III, B., Johnson, R. S., & Kahn, C. R. (1994) · Nature · doi:10.1038/372186a0 · Cited by 1,252
Self-citationCusi, K., Maezono, K., Osman, A., Pendergrass, M., Patti, M. E., Pratipanawatr, T., DeFronzo, R. A., Kahn, C. R., & Mandarino, L. J. (2000) · Journal of Clinical Investigation · doi:10.1172/jci7535 · Cited by 1,139
Self-citationUeki, K., Kondo, T., & Kahn, C. R. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.12.5434-5446.2004 · Cited by 686
Self-citationPGC-1 promotes insulin resistance in liver through PPAR-α-dependent induction of TRB-3
Koo, S.-H., Satoh, H., Herzig, S., Lee, C.-H., Hedrick, S., Kulkarni, R., Evans, R. M., Olefsky, J., & Montminy, M. (2004) · Nature Medicine · doi:10.1038/nm1044 · Cited by 550
Previs, S. F., Withers, D. J., Ren, J.-M., White, M. F., & Shulman, G. I. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m006490200 · Cited by 291
Site and mechanism of leptin action in a rodent form of congenital lipodystrophy
Asilmaz, E., Cohen, P., Miyazaki, M., Dobrzyn, P., Ueki, K., Fayzikhodjaeva, G., Soukas, A. A., Kahn, C. R., Ntambi, J. M., Socci, N. D., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200419511 · Cited by 210
Self-citationTripathy, D., Eriksson, K. F., Orho-Melander, M., Fredriksson, J., Ahlqvist, G., & Groop, L. (2004) · Diabetologia · doi:10.1007/s00125-004-1393-8 · Cited by 74
Cited by
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028
Critical nodes in signalling pathways: insights into insulin action
Taniguchi, C. M., Emanuelli, B., & Kahn, C. R. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1837 · Cited by 2,760
Self-citationSIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
Hirschey, M. D., Shimazu, T., Goetzman, E., Jing, E., Schwer, B., Lombard, D. B., Grueter, C. A., Harris, C., Biddinger, S., Ilkayeva, O. R., et al. (2010) · Nature · doi:10.1038/nature08778 · Cited by 1,687
Self-citationMicroRNAs in metabolism and metabolic disorders
Rottiers, V., & Näär, A. M. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3313 · Cited by 1,156
Dong, X. C., Copps, K. D., Guo, S., Li, Y., Kollipara, R., DePinho, R. A., & White, M. F. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.06.006 · Cited by 463
Metadata
- Authors
- Taniguchi, C. M., Ueki, K., & Kahn, C. R.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-03-01
- Volume
- 115
- Issue
- 3
- Pages
- 718-727
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2050941179
- Cited by
- 272
- References
- 9
- FWCI
- 8.41
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- bronze
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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