Telomere biology in cardiovascular disease - role of insulin sensitivity in diabetic hearts.

The present study examined telomere biology in the context of insulin sensitivity in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetic animal model. To improve insulin sensitivity, pioglitazone (PG; 10 mg/kg/day) was administered to OLETF rats between 20 weeks and 40 weeks of age, and the effects of the treatment were compared with those in untreated OLETF rats or control Long-Evans Tokushima Otsuka rats. The homeostasis model assessment of insulin resistance index significantly increased in OLETF rats, but decreased in PG-treated OLETF rats. Telomere lengths were not shortened in heart tissues of OLETF rats; however, telomerase activity was decreased in heart tissues of OLETF rats. Messenger RNA expression for both telomerase reverse transcriptase and telomere repeat binding factor 2 was downregulated in the hearts of OLETF rats. Protein expression of phosphorylated Akt, insulin-like growth factor and endothelial nitric oxide synthase were all reduced in OLETF rats. The changes observed in OLETF rats were inhibited by PG treatment. Myocardial fibrosis was less extensive and diastolic dysfunction improved in PG-treated OLETF rats versus untreated OLETF rats. These findings suggest that improving insulin sensitivity via the activation of peroxisome proliferator-activated receptor-gamma may exert regulatory effects on cardiac telomere biology, and may have desirable morphological and functional effects on the diabetic heart.