Roles of Obese-Insulin Resistance and Anti-Diabetic Drugs on the Heart with Ischemia-Reperfusion Injury

Abstract

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.

The impaired myocardial ischemic tolerance in adult offspring of diabetic pregnancy is restored by maternal melatonin treatment

“…MIR injury is characterized by oxidative stress, activation of apoptosis pathways, and enlargement of infarct size, which significantly contributes to long‐term mortality and heart failure post‐MI . Preexisting myocardial hypertrophy and glycemic dysregulation significantly exacerbate MIR injury . Of note, infants born to diabetic mothers are prone to develop myocardial hypertrophy, and increased prevalence of glucose intolerance or diabetes in adult offspring of diabetic pregnancy was reported, suggesting diabetic mother offspring may be more vulnerable to MIR injury, although further investigation is required.…”

Myocardial susceptibility to ischaemia/reperfusion in obesity: a re-evaluation of the effects of age

“…These results are in contrast with the many well-established age-related modifications in the cardiovascular system [1–3], but it should be kept in mind that our observations were made in healthy animals, without the comorbidities which may affect the outcome. There is also continued interest in the ability of cardioprotective interventions such as pre-or postconditioning to protect the ageing myocardium [1–4]. Our data showed that although aging hearts exhibited normal function under baseline conditions, with an unchanged response to I/R and retention of the capacity to reduce infarct size when preconditioned, this was associated with a reduction in the ability to recover functionality.…”

“…Possible signalling mechanisms involved in the effects of obese-insulin resistance have been reviewed by Apaijai and coworkers [4]. Unfortunately, as was the case in the outcome of the effects of I/R, no clear-cut pattern of changes emerged.…”

“…With regard to cardioprotection in the aging heart, a number of comprehensive reviews recently appeared [1–4] which indicated a loss in the ability to be preconditioned in the aging heart [27, 40, 53, 54]. For example, using infarct size as endpoint, Schulman and coworkers [31] showed that hearts from rats aged 18–20 months, could not be preconditioned by either multiple episodes of I/R or pharmacologically while the blunted response in middle-aged rat hearts could be improved by an increased preconditioning stimulus.…”

“…The respective contributions of the latter two factors have recently been extensively reviewed [1–4]. …”