Roles of Obese-Insulin Resistance and Anti-Diabetic Drugs on the Heart with Ischemia-Reperfusion Injury
- 444 Downloads
The incidence of obesity with insulin resistance is increasing worldwide. This condition is also known as a risk factor of coronary artery disease and associated with increased arrhythmias, impaired left ventricular function, and increased infarct size during cardiac ischemia-reperfusion (I/R) injury. The proposed mechanisms are due to impaired glucose utilization and pro-survival signaling molecules, and increased inflammatory cytokines, which have been demonstrated in the I/R hearts in various models of obese-insulin resistance. However, the cardiac effects of diets in the I/R heart are still unsettled since several studies reported that high-caloric diet consumption might protect the heart from I/R injury. Although several therapeutic strategies such as anti-diabetic drugs, natural compounds as well as treadmill exercise have been proposed to exert cardioprotection in the I/R heart in obese-insulin resistant animals, some interventions including ischemic post-conditioning failed to protect the heart from I/R injury. In this comprehensive review, reports from both genetic deletion and dietary-induced obese-insulin resistant animal models regarding the effects of obese-insulin resistance on metabolic parameters, cardiac function, infarct size, and molecular mechanisms under I/R injury are summarized. Moreover, the effects of anti-diabetic drugs and other pharmacological interventions on these parameters in an obese-insulin resistant model under I/R injury are also comprehensively summarized and discussed.
KeywordsObesity Left ventricular function Infarct size Ischemia-reperfusion injury Insulin resistance
This work was supported by the Thailand Research Fund Royal Golden Jubilee PhD Program (NC and NA), the Thailand Research Fund RTA5580006 (NC), BRG5780016 (SC), and the Chiang Mai University Excellent Center Award (NC).
Conflict of Interest
The authors declare that they have no conflict of interest.
- 1.Jequier E. Obesity. Impairment of energy intake or of energy expenditure. Ann Endocrinol (Paris). 1995;56(2):87–92.Google Scholar
- 9.Carillon J, Romain C, Bardy G, Fouret G, Feillet-Coudray C, Gaillet S, et al. Cafeteria diet induces obesity and insulin resistance associated with oxidative stress but not with inflammation: improvement by dietary supplementation with a melon superoxide dismutase. Free Radic Biol Med. 2013;65C:254–61.CrossRefGoogle Scholar
- 14.Honda T, Kaikita K, Tsujita K, Hayasaki T, Matsukawa M, Fuchigami S, et al. Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates myocardial ischemia-reperfusion injury in mice with metabolic disorders. J Mol Cell Cardiol. 2008;44(5):915–26.PubMedCrossRefGoogle Scholar
- 21.Nduhirabandi F, Du Toit EF, Blackhurst D, Marais D, Lochner A. Chronic melatonin consumption prevents obesity-related metabolic abnormalities and protects the heart against myocardial ischemia and reperfusion injury in a prediabetic model of diet-induced obesity. J Pineal Res. 2011;50(2):171–82.PubMedGoogle Scholar
- 54.Tanno M, Bassi R, Gorog DA, Saurin AT, Jiang J, Heads RJ, et al. Diverse mechanisms of myocardial p38 mitogen-activated protein kinase activation: evidence for MKK-independent activation by a TAB1-associated mechanism contributing to injury during myocardial ischemia. Circ Res. 2003;93(3):254–61.PubMedCrossRefGoogle Scholar
- 58.Andersson C, van Gaal L, Caterson ID, Weeke P, James WP, Coutinho W, et al. Relationship between HbA1c levels and risk of cardiovascular adverse outcomes and all-cause mortality in overweight and obese cardiovascular high-risk women and men with type 2 diabetes. Diabetologia. 2012;55(9):2348–55.PubMedCrossRefGoogle Scholar
- 61.Lee SH, Park JS, Kim W, Shin DG, Kim YJ, Kim DS, et al. Impact of body mass index and waist-to-hip ratio on clinical outcomes in patients with ST-segment elevation acute myocardial infarction (from the Korean acute myocardial infarction registry). Am J Cardiol. 2008;102(8):957–65.PubMedCrossRefGoogle Scholar
- 65.Choy B, Hansen E, Moss AJ, McNitt S, Zareba W, Goldenberg I. Relation of body mass index to sudden cardiac death and the benefit of implantable cardioverter-defibrillator in patients with left ventricular dysfunction after healing of myocardial infarction. Am J Cardiol. 2010;105(5):581–6.PubMedCrossRefGoogle Scholar
- 70.Khattab AA, Daemen J, Richardt G, Rioux P, Amann FW, Levy R, et al. Impact of body mass index on the one- year clinical outcome of patients undergoing multivessel revascularization with sirolimus-eluting stents (from the arterial revascularization therapies study part II). Am J Cardiol. 2008;101(11):1550–9.PubMedCrossRefGoogle Scholar