Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression Changes

Abstract

Despite clinical studies indicating that diabetic hearts are more sensitive to ischemia/reperfusion injury, experimental data is contradictory. Although mild diabetes prior to ischemia/reperfusion may induce a myocardial adaptation, further research is still needed. Nondiabetic Wistar (W) and type 2 diabetic Goto-Kakizaki (GK) rats (16-week-old) underwent 45 min occlusion of the left anterior descending coronary artery and 24 h reperfusion. The plasma glucose level was significantly higher in diabetic rats compared to the nondiabetics. Diabetes mellitus was associated with ventricular hypertrophy and increased interstitial fibrosis. Inducing myocardial infarction increased the glucose levels in diabetic compared to nondiabetic rats. Furthermore, the infarct size was smaller in GK rats than in the control group. Systolic and diastolic functions were impaired in W + MI and did not reach statistical significance in GK + MI animals compared to the corresponding controls. Among the 125 genes surveyed, 35 genes showed a significant change in expression in GK + MI compared to W + MI rats. Short-term diabetes promotes compensatory mechanisms that may provide cardioprotection against ischemia/reperfusion injury, at least in part, by increased antioxidants and the upregulation of the prosurvival PI3K/Akt pathway, by the downregulation of apoptotic genes, proinflammatory cytokine TNF-α, profibrogenic TGF-β, and hypertrophic marker α-actin-1.

Diabetic animal fed with high‐fat diet prevents the protective effect of myocardial ischemic preconditioning effect in isolated rat heart perfusion model

“…In addition, higher I/R injury and corresponding less IPC‐mediated protection in DCM, when compared with the DM heart in the present study, account for the influence of metabolic changes induced by an HFD that induced structural changes in the myocardium. In agreement with the previous preclinical trial, [ 34 ] DM heart showed comparatively less infarct size and better hemodynamics than normal and DCM heart, emphasizing the infarct sparing effect of DM against I/R.…”

Transcriptomic alterations in the heart of non-obese type 2 diabetic Goto-Kakizaki rats

“…The metabolic features manifested in this animal model are in many ways similar to the pathogenesis of inherited spontaneous T2DM in humans [ 29 , 32 ]. However, hyperglycemia and glucose intolerance developed in GK rats are not associated with the development of obesity or hypertension [ 1 ]. The adult GK rat of T2DM has been shown to develop cardiovascular complications including left ventricular hypertrophy, fibrosis, as well as diastolic and/or systolic dysfunction [ 1 , 20 , 35 , 36 ].…”

“…Diabetes mellitus is a heterogeneous chronic metabolic disorder characterized by hyperglycemia as a common feature resulting from impaired insulin secretion, insulin resistance, or both [ 1 ]. In 2014, the global prevalence of diabetes mellitus (DM) was estimated to be 9 % among adults according to WHO data [ 2 ].…”

“…The total number of people suffering from DM is projected to almost triple from 190 million to 552 million by 2030 [ 3 , 4 ]. T2DM accounts for more than 90 % of all diabetes cases and its incidence is continuously rising worldwide [ 1 , 5 , 6 ]. The major cause for this phenomenon is the so-called obesity epidemic due to physical inactivity and increased consumption of energy-rich food [ 7 ].…”

Role of adiponectin in diabetes myocardial ischemia-reperfusion injury and ischemic postconditioning

“…Over the last decades, diabetes mellitus (DM) has aroused increasing attention globally 1 . Ischemic heart disease is a major cardiovascular complication of diabetes and the primary cause of mortality in diabetic disease 2 . A number of studies have confirmed that compared with non-diabetic patients, patients with diabetes were susceptible to myocardial ischemia-reperfusion injury, and have poor treatment effect 3 .…”