Akademik Veri Yönetim Sistemi
5. Uluslararası, 34. Ulusal Biyofizik Kongresi, İzmir, Türkiye, 6 - 09 Eylül 2023, ss.257-258, (Özet Bildiri)
Aim: Concomitant occurrence of health conditions such as obesity, insulin resistance, dyslipidaemia, and hypertension can increase the risk of diabetes type 2 and cardiomyopathy. Metabolic syndrome-associated cardiomyopathy is increasingly common worldwide leading to a massive socioeconomic boredom on the individuals and society. Sirtuins, NAD+ dependent deacetylases, can improve the mitochondrial biogenesis and are of importance in therapeutic interventions. As decreased of the sirtuins levels have been observed in metabolic syndrome associated cardiomyopathy, this study aimed to investigate the functions of sirtuins in palmitat-induced insulin resistant H9C2 cell lines.
Materials and Method: Insulin resistance was established in H9c2 cells using palmitic acid incubation (50μM for 24h). The development of Insulin resistance in cells was verified by monitoring the cellular 2- DG6P uptake assays in these treated cells. Control and Insulin resistant H9c2 cells were incubated with nicotinamide (NAM, an inhibitor of sirtuins; 20mM for 24h) or NAD+ precursors nicotinamide mononucleotide (NMN; 2mM for 24h) to increase or decrease lysine (K)-acetylation, respectively. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were monitored with confocal imaging using a ratiometric JC-1 (5µM) and ROS-sensitive DCFDA (10µM) fluorescent dyes, respectively. Total K-acetylation was determined by using western blot analysis.
Results: Higher ROS level and depolarized MMP were observed in palmitic acid induced insulin resistant cells in comparison to controls. Elevated K-acetylation with NAM showed exacerbated ROS levels and depolarized MMP. However, incubation of insulin resistant cells with NMN ameliorated the ROS levels, Kacetylation and MMP. Likewise, inhibition of sirtuins markedly increased the total protein K-acetylation and ROS level and depolarized the MMP.
Conclusions: Therefore, one can suggest that sirtuin activation, as a novel regulator, can provide direct cardio-protection in the insulin resistant heart, can be a good candidate as a new drug for the treatment of insulin resistant-associated cardiovascular disorders.