2. Academic Validation
  3. Glucose fluctuations aggravate myocardial fibrosis via activating the CaMKII/Stat3 signaling in type 2 diabtetes

Glucose fluctuations aggravate myocardial fibrosis via activating the CaMKII/Stat3 signaling in type 2 diabtetes

  • Diabetol Metab Syndr. 2023 Oct 28;15(1):217. doi: 10.1186/s13098-023-01197-5.
Lei Zhang # 1,  Huan-Huan Liu # 2,  Fan Yang 1,  Zhi-Yuan Zhang 1,  Zhen-Ye Zhang 1,  Xiao-Xi Zhao 1,  Ling-Ling Qian 1,  Shi-Peng Dang 3,  Ru-Xing Wang 4
Affiliations

Affiliations

  • 1 Department of Cardiology, Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, China.
  • 2 Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China.
  • 3 Department of Cardiology, Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, China. [email protected].
  • 4 Department of Cardiology, Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, China. [email protected].
  • # Contributed equally.
PMID: 37891701 DOI: 10.1186/s13098-023-01197-5
Abstract

Background: Glucose fluctuations (GF) are a risk factor for cardiovascular complications associated with type 2 diabetes. However, there is a lack of adequate research on the effect of GF on myocardial fibrosis and the underlying mechanisms in type 2 diabetes. This study aimed to investigate the impact of glucose fluctuations on myocardial fibrosis and explore the potential mechanisms in type 2 diabetes.

Methods: Sprague Dawley (SD) rats were randomly divided into three groups: the control (Con) group, the type 2 diabetic (DM) group and the glucose fluctuations (GF) group. The type 2 diabetic rat model was established using a high-fat diet combined with low-dose streptozotocin injection and the GF model was induced by using staggered glucose and Insulin injections daily. After eight weeks, echocardiography was used to assess the cardiac function of the three groups. Hematoxylin-eosin and Masson staining were utilized to evaluate the degree of pathological damage and fibrosis. Meanwhile, a neonatal rat cardiac fibroblast model with GF was established. Western and immunofluorescence were used to find the specific mechanism of myocardial fibrosis caused by GF.

Results: Compared with rats in the Con and the DM group, cardiac function in the GF group showed significant impairments. Additionally, the results showed that GF aggravated myocardial fibrosis in vitro and in vivo. Moreover, Ca2+/calmodulin‑dependent protein kinase II (CaMKII) was activated by phosphorylation, prompting an increase in phosphorylation of signal transducer and activator of transcription 3 (STAT3) and induced nuclear translocation. Pretreatment with KN-93 (a CaMKII inhibitor) blocked GF-induced STAT3 activation and significantly suppressed myocardial fibrosis.

Conclusions: Glucose fluctuations exacerbate myocardial fibrosis by triggering the CaMKII/STAT3 pathway in type 2 diabetes.

Keywords

CaMKII; Glucose fluctuations; Myocardial fibrosis; Stat3.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
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  • HY-15465
    99.19%, CaMK II Inhibitor‎