Dipeptidylpeptidase inhibition is associated with improvement in blood pressure and diastolic function in insulin-resistant male Zucker obese rats.

摘要: Diastolic dysfunction is a prognosticator for future cardiovascular events that demonstrates strong correlation with obesity. Pharmacological inhibition of dipeptidylpeptidase-4 (DPP-4) to increase the bioavailability glucagon-like peptide-1 an emerging therapy control glycemia in type 2 diabetes patients. Accumulating evidence suggests has insulin-independent actions tissue. However, it not known whether DPP-4 improves obesity-related diastolic dysfunction. Eight-week-old Zucker obese (ZO) and lean rats were fed normal chow diet or containing inhibitor, linagliptin (LGT), 8 weeks. Plasma activity was 3.3-fold higher ZO compared reduced by 95% LGT treatment. improved echocardiographic pressure volume-derived indices function impaired rats, without altering food intake body weight gain during study period. also blunted elevated blood progression involving skeletal muscle arteriolar function, reducing left ventricular hypertrophy, fibrosis, oxidative stress hearts. Expression phosphorylated- endothelial nitric oxide synthase (eNOS)(Ser1177), total eNOS, sarcoplasmic reticulum calcium ATPase 2a protein LGT-treated heart, suggesting Ca(2+) handling. The myocardium had abnormal mitochondrial sarcomeric arrangement cristae structure normalized LGT. These studies suggest reduces intracellular Cai(2+) mishandling cardiomyocyte ultrastructure, which collectively result improvements absence reductions insulin-resistant rats.