D‐pinitol alleviates diabetic cardiomyopathy by inhibiting the optineurin‐mediated endoplasmic reticulum stress and glycophagy signaling pathway

• DOI: 10.1002/ptr.8134
• Publication Date: 2024-02-05T00:34:28Z
• Authors: Xiaoli Li; Xin Yu; Fei Yu; Chunli Fu; Wenqian Zhao; Xiaosong Liu; Chaochao Dai; Haiqing Gao; Mei Cheng; Baoying Li
• Keywords: Diabetic Cardiomyopathy; Cardiac Fibrosis; Optineurin

Abstract Diabetic cardiomyopathy (DCM) is an important complication resulting in heart failure and death of diabetic patients. However, there no effective drug for treatments. This study investigated the effect D‐pinitol (DP) on cardiac injury using mice glycosylation cardiomyocytes its molecular mechanisms. We established streptozotocin‐induced SAMR1 SAMP8 DP (150 mg/kg/day) intragastrically advanced glycation end‐products (AGEs)‐induced H9C2 cells. cells were transfected with optineurin (OPTN) siRNA overexpression plasmids. The metabolic disorder indices, dysfunction, histopathology, immunofluorescence, western blot, immunoprecipitation investigated. Our results showed that reduced blood glucose AGEs, increased expression OPTN cells, thereby inhibiting endoplasmic reticulum stress (GRP78, CHOP) glycophagy (STBD1, GABARAPL1), alleviating myocardial apoptosis fibrosis DCM. filamin A as interaction protein downregulated by AGEs decreased abundance. Moreover, GRP78, CHOP, STBD1, GABARAPL1 inhibited GAA via GSK3β phosphorylation FoxO1. may be helpful to treat onset Targeting could translated into clinical application fighting against