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

Q: What is the clinical evidence from this study?

Population: Type 2 diabetes and myocardial fibrosis (n=45). Intervention: Glucose fluctuations vs. Control group and type 2 diabetic group without glucose fluctuations. Primary outcome: Myocardial fibrosis and cardiac function (p=<0.05).

Lei Zhang; Huan‐Huan Liu; Fan Yang; Zhiyuan Zhang; Zhen‐Ye Zhang; Xiaoxi Zhao; Lingling Qian; Shipeng Dang; Ruxing Wang

doi:10.1186/s13098-023-01197-5

October 28, 2023Diabetology & Metabolic SyndromeOpen Access

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

View Full Paper

Ask AI

Bookmark

Share

Key result

Glucose fluctuations exacerbated myocardial fibrosis and cardiac dysfunction in type 2 diabetic rats by triggering the CaMKII/Stat3 signaling pathway.

Figures

Why the study?

There is a lack of adequate research on the effect of glucose fluctuations on myocardial fibrosis and the underlying mechanisms in type 2 diabetes.

Do glucose fluctuations exacerbate myocardial fibrosis via the CaMKII/Stat3 pathway in type 2 diabetes models?

Structured PICO

Do glucose fluctuations exacerbate myocardial fibrosis via the CaMKII/Stat3 pathway in type 2 diabetes models?

P

Population

45 male Sprague-Dawley rats, aged 6-8 weeks, were used to model type 2 diabetes and glucose fluctuations over an 8-week period to study myocardial fibrosis.

I

Intervention

Glucose fluctuations (GF) induced by daily staggered glucose and insulin injections for 8 weeks (in vivo) or alternating 5.5 and 33 mmol/L glucose every 12 hours for 72 hours (in vitro).

C

Comparator

Control group (normal diet/normal glucose) and diabetic group without glucose fluctuations (high-fat diet/high glucose).

O

Outcome

Degree of myocardial fibrosis (evaluated by HE/Masson staining and Collagen I, Collagen III, TGF-β1 expression) and cardiac function (EF, FS, LVIDd, LVIDs) at 8 weeks.surrogate

Main Result

p-value: p=<0.05

Glucose fluctuations exacerbate myocardial fibrosis and cardiac dysfunction in type 2 diabetes models by activating the CaMKII/Stat3 signaling pathway.

Limitations

Only investigated the role of CaMKII/Stat3 in regulating myocardial fibrosis with inhibitors at the cellular level instead of the animal level.
Only used the inhibitor KN-93 to explore the underlying mechanisms, and did not use other inhibitors of CaMKII or knockout animals.
Investigated the role of CaMKII/Stat3 in regulating myocardial fibrosis with inhibitors only at the cellular level instead of the animal level.
Only used the inhibitor KN-93 to explore underlying mechanisms, and did not use other inhibitors of CaMKII or knockout animals.

Implication

Should not alter clinical glucose management in T2D; leaves open CaMKII/Stat3 targeting for future human studies.

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: /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.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Zhang et al. (2023) studied Type 2 diabetes and myocardial fibrosis (n=45). Glucose fluctuations vs. Control group and type 2 diabetic group without glucose fluctuations was evaluated on Myocardial fibrosis and cardiac function (p=<0.05). Glucose fluctuations exacerbated myocardial fibrosis and cardiac dysfunction in type 2 diabetic rats by triggering the CaMKII/Stat3 signaling pathway.

synapsesocial.com/papers/6a8c0945f19228bbb2fb6d85 https://doi.org/10.1186/s13098-023-01197-5

View Full Paper

Ask AI

Bookmark

Share

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

Figures

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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

Figures

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading