Effect of intervention in the diacylglycerol-protein kinase C signaling pathway on JNK1 expression and its downstream signaling in diabetic cardiomyopathy

Abstract

This study aimed to investigate the expression of signaling molecules, such as c-Jun N-terminal kinase 1 (JNK1) and insulin receptor substrate 1 (IRS1), in the myocardium of diabetic rats following intervention in the diacylglycerol-protein kinase C (DAG-PKC) signal transduction pathway. The rats were divided into three groups, the diabetic model, control and breviscapine-treated diabetes (intervention) group. Following modeling and drug treatment, hematoxylin and eosin (HE) and Masson staining and electron microscopy were used to observe the pathological changes in the rat myocardium. The expression of PKC-β2, JNK1, and IRS1 was assessed in rat myocardium by immunohistochemistry and quantitative polymerase chain reaction (qPCR). The expression levels of PKC-β2, JNK1, phosphorylated JNK (p-JNK) and IRS1 in the diabetic model group were significantly higher than those in the control group. Furthermore, compared with the diabetic model group, expression levels of PKC-β2, JNK1, p-JNK and IRS1 were significantly reduced following intervention in the DAG-PKC signal transduction pathway. The DAG-PKC pathway may affect downstream signaling through JNK1 (the common signal point of the G-protein receptor pathway and insulin receptor pathway at the cell membrane) to result in the occurrence and development of diabetic cardiomyopathy (DCM). The series of signal points DAG-PKC-JNK1-IRS1-Akt/PKB-mTOR-p70S6K1 is a potential pathway for inducing DCM by DAG-PKC signal transduction. Enhanced expression of JNK1, p-JNK and IRS1 may accelerate diabetic myocardial fibrosis.