title: 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.
authors.affiliation: Department of Emergency Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Fengtian Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110000, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Qi
authors.affiliation: Department of Emergency Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000209:etiology* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004075:Diglycerides / Q000378:metabolism*; D004195:Disease Models, Animal; D005419:Flavonoids / Q000627:therapeutic use; D005786:Gene Expression Regulation; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C011439:1,2-diacylglycerol; D004075:Diglycerides; D005419:Flavonoids; D055504:Insulin Receptor Substrate Proteins; C061097:breviscapine; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D048055:Mitogen-Activated Protein Kinase 8