The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Nitric Oxide Mediates the Antiapoptotic Effect of Insulin in Myocardial Ischemia-Reperfusion: The Roles of PI3-Kinase, Akt , and Endothelial Nitric Oxide Synthase Phosphorylation
Open accessAbstract
Background— Recent evidence from cultured endothelial cell studies suggests that phosphorylation of endothelial nitric oxide synthase (eNOS) through the PI3-kinase– Akt pathway increases NO production. This study was designed to elucidate the signaling pathway involved in the antiapoptotic effect of insulin in vivo and to test the hypothesis that phosphorylation of eNOS by insulin may participate in the cardioprotective effect of insulin after myocardial ischemia and reperfusion. Methods and Results— Male Sprague-Dawley rats were subjected to 30 minutes of myocardial ischemia and 4 hours of reperfusion. Rats were randomized to receive vehicle, insulin, insulin plus wortmannin, or insulin plus L-NAME. Treatment with insulin resulted in 2.6-fold and 4.3-fold increases in Akt and eNOS phosphorylation and a significant increase in NO production in ischemic/reperfused myocardial tissue. Phosphorylation of Akt and eNOS and increase of NO production by insulin were completely blocked by wortmannin, a PI3-kinase inhibitor. Pretreatment with L-NAME, a nonselective NOS inhibitor, had no effect on Akt and eNOS phosphorylation but significantly reduced NO production. Moreover, treatment with insulin markedly reduced myocardial apoptotic death ( P <0.01 versus vehicle). Pretreatment with wortmannin abolished the antiapoptotic effect of insulin. Most importantly, pretreatment with L-NAME also significantly reduced the antiapoptotic effect of insulin ( P <0.01 versus insulin). Conclusions— These results demonstrated that in vivo administration of insulin activated Akt through the PI3-kinase–dependent mechanism and reduced postischemic myocardial apoptotic death. Phosphorylation of eNOS and the concurrent increase of NO production contribute significantly to the antiapoptotic effect of insulin.
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Cites
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Cited by
Cardiovascular Actions of Insulin
Muniyappa, R., Montagnani, M., Koh, K. K., & Quon, M. J. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0006 · Cited by 872
Kempf, T., Eden, M., Strelau, J., Naguib, M., Willenbockel, C., Tongers, J., Heineke, J., Kotlarz, D., Xu, J., Molkentin, J. D., et al. (2006) · Circulation Research · doi:10.1161/01.res.0000202805.73038.48 · Cited by 651
Nitric Oxide and Cardiac Function: Ten Years After, and Continuing
Massion, P. B., Feron, O., Dessy, C., & Balligand, J.-L. (2003) · Circulation Research · doi:10.1161/01.res.0000088351.58510.21 · Cited by 567
Regulation of endothelial and myocardial NO synthesis by multi-site eNOS phosphorylation
Mount, P. F., Kemp, B. E., & Power, D. A. (2007) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2006.05.023 · Cited by 498
Balligand, J.-L., Feron, O., & Dessy, C. (2009) · Physiological Reviews · doi:10.1152/physrev.00042.2007 · Cited by 477
Metadata
- Authors
- Gao, F., Gao, E., Yue, T.-L., Ohlstein, E. H., Lopez, B. L., Christopher, T. A., & Ma, X.-L.
- Venue
- Circulation
- Published
- 2002-03-26
- Volume
- 105
- Issue
- 12
- Pages
- 1497-1502
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2022131685
- Cited by
- 469
- References
- 30
- FWCI
- 18.07
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Gao, F., Gao, E., Yue, T.-L., Ohlstein, E. H., Lopez, B. L., Christopher, T. A., & Ma, X.-L. (2002). Nitric Oxide Mediates the Antiapoptotic Effect of Insulin in Myocardial Ischemia-Reperfusion: The Roles of PI3-Kinase, Akt , and Endothelial Nitric Oxide Synthase Phosphorylation. Circulation. https://doi.org/10.1161/01.cir.0000012529.00367.0f
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