Phosphoproteomics analysis of diabetic cardiomyopathy in aging-accelerated mice and effects of D-pinitol.

PURPOSE The molecular mechanisms of diabetic cardiomyopathy (DCM) development and D-pinitol (DP) in its treatment remain unclear. The present study is to explore the underlying mechanism of DCM in an elderly diabetic mouse model and to seek the protective targets of DP by phosphoproteomics. EXPERIMENTAL DESIGN We used streptozotocin to induce diabetes in SAMP8 and DP (150 mg/kg/day) intragastrically administrated to diabetic mice for 8 weeks. The heart tissues were harvested for label-free phosphoproteomic analysis from diabetic mice. Some differentially regulated phosphorylation sites were confirmed by parallel reaction monitoring. RESULTS Our results showed that 612 phosphorylation sites on 454 proteins had their phosphorylation levels significantly changed in the heart of untreated diabetic mice (DM). Of these phosphorylation sites, 216 phosphorylation sites on 182 proteins were normalized after DP treatment. We analyzed the functional signaling pathways in the heart of DP treated diabetic mice (DMT), including glucagon signaling pathway, insulin signaling pathway, mitophagy, apoptosis, and longevity regulating pathway. Two consensus motifs identified were targeted by Src and epidermal growth factor receptor between DMT and DM groups. CONCLUSIONS AND CLINICAL RELEVANCE Our study might help to better understand the mechanism of DCM, provide novel targets for estimating the protective effects of DP.