Key result
Alogliptin attenuated left ventricular hypertrophy, left atrial dilation, and atrial fibrillation inducibility in diabetic rabbits while improving mitochondrial function and biogenesis.
Why the study?
Does alogliptin prevent atrial fibrillation inducibility and mitochondrial dysfunction in a diabetic rabbit model?
RCT (n=90)
randomized
Does alogliptin prevent atrial fibrillation inducibility and mitochondrial dysfunction in a diabetic rabbit model?
Alogliptin prevents atrial remodeling and reduces atrial fibrillation inducibility in diabetic rabbits by improving mitochondrial function and biogenesis.
*Clause 2 (Research meaning):* leaves open whether these mitochondrial mechanisms translate.
BACKGROUND: There is increasing evidence implicating atrial mitochondrial dysfunction in the pathogenesis of atrial fibrillation. In this study, we explored whether alogliptin, a dipeptidyl peptidase-4 inhibitor, can prevent mitochondrial dysfunction and atrial remodeling in a diabetic rabbit model. METHODS AND RESULTS: A total of 90 rabbits were randomized into 3 groups as follows: control group (n=30), alloxan-induced diabetes mellitus group (n=30), and alogliptin-treated (12.5 mg/kg per day for 8 weeks) diabetes mellitus group (n=30). Echocardiographic and hemodynamic assessments were performed in vivo. The serum concentrations of glucagon-like peptide-1, insulin, and inflammatory and oxidative stress markers were measured. Electrophysiological properties of Langendorff-perfused rabbit hearts were assessed. Mitochondrial morphology, respiratory function, membrane potential, and reactive oxygen species generation rate were assessed. The protein expression of transforming growth factor β1, nuclear factor κB p65, and mitochondrial biogenesis-related proteins were measured by Western blot analysis. Diabetic rabbits exhibited left ventricular hypertrophy and left atrial dilation without obvious hemodynamic abnormalities, and all of these changes were attenuated by alogliptin. Compared with the control group, higher atrial fibrillation inducibility in the diabetes mellitus group was observed, and markedly reduced by alogliptin. Alogliptin decreased mitochondrial reactive oxygen species production rate, prevented mitochondrial membrane depolarization, and alleviated mitochondrial swelling in diabetic rabbits. It also improved mitochondrial biogenesis by peroxisome proliferator-activated receptor-γ coactivator 1α/nuclear respiratory factor-1/mitochondrial transcription factor A signaling regulated by adiponectin/AMP-activated protein kinase. CONCLUSIONS: Dipeptidyl peptidase-4 inhibitors can prevent atrial fibrillation by reversing electrophysiological abnormalities, improving mitochondrial function, and promoting mitochondrial biogenesis.
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Zhang et al. (2017) conducted an RCT in diabetes mellitus (n=90). Alogliptin vs. alloxan-induced diabetes mellitus group and control group was evaluated on atrial fibrillation inducibility and mitochondrial function. Alogliptin attenuated left ventricular hypertrophy, left atrial dilation, and atrial fibrillation inducibility in diabetic rabbits while improving mitochondrial function and biogenesis.
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