The Insulin Sensitizer Pioglitazone Improves the Deterioration of Ischemic Preconditioning in Type 2 Diabetes Mellitus Rats

Abstract

SUMMARYWe investigated the effects of ischemic preconditioning (IP) on reperfusion arrhythmias in type 2 diabetic rats as well as the effects of the insulin sensitizer pioglitazone. Thirty-week-old OLETF rats with or without pioglitazone (10 mg/kgBW, orally) were used as a model for type 2 diabetes. LETO rats served as controls. The incidences and durations of reperfusion ventricular tachyarrhythmias (RVT) were evaluated using a working heart method. After 5 minutes of initial perfusion, the rats were divided into the following groups: 1) control rats without IP (CIP(-)), 2) control rats with IP (CIP(+)), 3) diabetic rats without IP (DIP(-)), 4) diabetic rats with IP (DIP(+)), 5) pioglitazone-treated diabetic rats without IP (TDIP(-)), and 6) pioglitazone-treated diabetic rats with IP (TDIP(+)). Three 2-minute cycles of global diastolic ischemia and 5 minutes of reperfusion before long ischemia were performed as IP. The incidence and duration of RVT in CIP(+) were significantly lower than in CIP(-). There was no significant difference in the duration of RVT between DIP(+) and DIP(-). However, the duration of RVT in TDIP(+) was significantly shorter than TDIP(-). These results suggested that the effects of IP on reperfusion arrhythmias are deteriorated in type 2 diabetic rats. The insulin sensitizer pioglitazone can improve the deterioration of IP against reperfusion arrhythmias in type 2 diabetic rats. (Int Heart J 2007; 48: 623-635)

Effect of Pretreatment With Pioglitazone on Reperfusion Injury in Diabetic Patients With Acute Myocardial Infarction

“…Moreover, it exerted antiapoptic effects in cardiomyocytes by the activation of Akt, 13-15 and reduced ischemia-reperfusion arrhythmias and myocardial infarct size via the opening of mitochondrial adenosine triphosphate sensitive potassium channels. 13,15,25 In the present study, pretreatment with PIO resulted in a higher percentage of the blush score ≥2 and a complete ST resolution, and reperfusion arrhythmias were unlikely to be induced in the PIO group. In addition, these results were still observed even after adjusted for the difference in plasma glucose level on admission between the 2 groups.…”

Myocardial postconditioning: Next step to cardioprotection

“…Numerous pathological states such as hyperglycemia, hypercholesterolemia, hypertension, atherosclerosis, heart failure and aging have been suggested to modify the preconditioning response (Yellon and Downey, 2003;Hassouna et al, 2006;Sasaki et al, 2007). A range of studies have also investigated the modulatory role of various pathological states in the setting of IPost.…”

Beta-glucans in the treatment of diabetes and associated cardiovascular risks

“…It is also caused by the impaired PI3K/Akt pathway (Shulman 2000; Kim et al 2001). Insulin sensitizer has been demonstrated to be beneficial (Sasaki et al 2007). Thus, beta-glucan induction of PI3K/Akt to sensitise insulin could be important for the prevention of cardiomyopathy in diabetes.…”