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Insulin attenuates myocardial ischemia/reperfusion injury via reducing oxidative/nitrative stress.
Am J Physiol Endocrinol Metab. 2010 Apr; 298(4):E871-80.AJ

Abstract

It is well known that insulin possesses a cardioprotective effect and that insulin resistance is closely related to cardiovascular diseases. Peroxynitrite (ONOO(-)) formation may trigger oxidative/nitrative stress and represent a major cytotoxic effect in heart diseases. This study was designed to investigate whether insulin attenuates ONOO(-) generation and oxidative/nitrative stress in acute myocardial ischemia/reperfusion (MI/R). Adult male rats were subjected to 30 min of myocardial ischemia and 3 h of reperfusion. Rats randomly received vehicle, insulin, or insulin plus wortmannin. Arterial blood pressure and left ventricular pressure were monitored throughout the experiment. Insulin significantly improved cardiac functions and reduced myocardial infarction, apoptotic cell death, and blood creatine kinase/lactate dehydrogenase levels following MI/R. Myocardial ONOO(-) formation was significantly attenuated after insulin treatment. Moreover, insulin resulted in a significant increase in Akt and endothelial nitric oxide (NO) synthase (eNOS) phosphorylation, NO production, and antioxidant capacity in ischemic/reperfused myocardial tissue. On the other hand, insulin markedly reduced MI/R-induced inducible NOS (iNOS) and gp91(phox) expression in cardiac tissue. Inhibition of insulin signaling with wortmannin not only blocked the cardioprotection of insulin but also markedly attenuated insulin-induced antioxidative/antinitrative effect. Furthermore, the suppression on ONOO(-) formation by either insulin or an ONOO(-) scavenger uric acid reduced myocardial infarct size in rats subjected to MI/R. We concluded that insulin exerts a cardioprotective effect against MI/R injury by blocking ONOO(-) formation. Increased physiological NO production (via eNOS phosphorylation) and superoxide anion reduction contribute to the antioxidative/antinitrative effect of insulin, which can be reversed by inhibiting phosphatidylinositol 3'-kinase. These results provide important novel information on the mechanisms of cardiovascular actions of insulin.

Authors+Show Affiliations

Dept. of Physiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20124508

Citation

Ji, Lele, et al. "Insulin Attenuates Myocardial Ischemia/reperfusion Injury Via Reducing Oxidative/nitrative Stress." American Journal of Physiology. Endocrinology and Metabolism, vol. 298, no. 4, 2010, pp. E871-80.
Ji L, Fu F, Zhang L, et al. Insulin attenuates myocardial ischemia/reperfusion injury via reducing oxidative/nitrative stress. Am J Physiol Endocrinol Metab. 2010;298(4):E871-80.
Ji, L., Fu, F., Zhang, L., Liu, W., Cai, X., Zhang, L., Zheng, Q., Zhang, H., & Gao, F. (2010). Insulin attenuates myocardial ischemia/reperfusion injury via reducing oxidative/nitrative stress. American Journal of Physiology. Endocrinology and Metabolism, 298(4), E871-80. https://doi.org/10.1152/ajpendo.00623.2009
Ji L, et al. Insulin Attenuates Myocardial Ischemia/reperfusion Injury Via Reducing Oxidative/nitrative Stress. Am J Physiol Endocrinol Metab. 2010;298(4):E871-80. PubMed PMID: 20124508.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin attenuates myocardial ischemia/reperfusion injury via reducing oxidative/nitrative stress. AU - Ji,Lele, AU - Fu,Feng, AU - Zhang,Lihua, AU - Liu,Wenchong, AU - Cai,Xiaoqing, AU - Zhang,Lei, AU - Zheng,Qiangsun, AU - Zhang,Haifeng, AU - Gao,Feng, Y1 - 2010/02/02/ PY - 2010/2/4/entrez PY - 2010/2/4/pubmed PY - 2010/4/14/medline SP - E871 EP - 80 JF - American journal of physiology. Endocrinology and metabolism JO - Am J Physiol Endocrinol Metab VL - 298 IS - 4 N2 - It is well known that insulin possesses a cardioprotective effect and that insulin resistance is closely related to cardiovascular diseases. Peroxynitrite (ONOO(-)) formation may trigger oxidative/nitrative stress and represent a major cytotoxic effect in heart diseases. This study was designed to investigate whether insulin attenuates ONOO(-) generation and oxidative/nitrative stress in acute myocardial ischemia/reperfusion (MI/R). Adult male rats were subjected to 30 min of myocardial ischemia and 3 h of reperfusion. Rats randomly received vehicle, insulin, or insulin plus wortmannin. Arterial blood pressure and left ventricular pressure were monitored throughout the experiment. Insulin significantly improved cardiac functions and reduced myocardial infarction, apoptotic cell death, and blood creatine kinase/lactate dehydrogenase levels following MI/R. Myocardial ONOO(-) formation was significantly attenuated after insulin treatment. Moreover, insulin resulted in a significant increase in Akt and endothelial nitric oxide (NO) synthase (eNOS) phosphorylation, NO production, and antioxidant capacity in ischemic/reperfused myocardial tissue. On the other hand, insulin markedly reduced MI/R-induced inducible NOS (iNOS) and gp91(phox) expression in cardiac tissue. Inhibition of insulin signaling with wortmannin not only blocked the cardioprotection of insulin but also markedly attenuated insulin-induced antioxidative/antinitrative effect. Furthermore, the suppression on ONOO(-) formation by either insulin or an ONOO(-) scavenger uric acid reduced myocardial infarct size in rats subjected to MI/R. We concluded that insulin exerts a cardioprotective effect against MI/R injury by blocking ONOO(-) formation. Increased physiological NO production (via eNOS phosphorylation) and superoxide anion reduction contribute to the antioxidative/antinitrative effect of insulin, which can be reversed by inhibiting phosphatidylinositol 3'-kinase. These results provide important novel information on the mechanisms of cardiovascular actions of insulin. SN - 1522-1555 UR - https://www.unboundmedicine.com/medline/citation/20124508/Insulin_attenuates_myocardial_ischemia/reperfusion_injury_via_reducing_oxidative/nitrative_stress_ L2 - https://journals.physiology.org/doi/10.1152/ajpendo.00623.2009?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -