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Updated: Jun 5, 2025
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Yanjiani Xu1, Jialiang Zhang2, Jing Zhou1
1Department of Cardiology, West China Hospital, Sichuan University; Laboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University; Cardiac Structure and Function Research Key Laboratory of Sichuan Province, West China Hospital, Sichuan University.
Abstract:
The underlying pathophysiological mechanisms of diabetic cardiomyopathy (DbCM), a leading cause of mortality among patients with type 2 diabetes mellitus (T2DM), remain poorly understood. The myocardial toxicity associated with T2DM is attributed to factors such as lipotoxicity, glucotoxicity, oxidative stress, reduced cardiac efficiency, and lipoapoptosis. Compared to rats, mice offer greater accessibility, cost-effectiveness, and broader applicability for animal experiments. Insulin resistance and impaired insulin secretion are crucial factors in the pathophysiology of T2DM. We introduce a novel nongenetic murine model that replicates the progression of human DbCM induced by a combination of high-fat diet (HFD) feeding and streptozotocin (STZ) injection. In this study, we used wild-type C57BL/6J mice, administering an HFD regimen for 12 weeks, followed by intraperitoneal injections of STZ for an additional 12 weeks to induce characteristic manifestations of T2DM. We conducted oral glucose tolerance tests and measured serum insulin concentrations to confirm the development of insulin resistance and insufficient insulin secretion. Cardiac structure and function were rigorously assessed through noninvasive transthoracic echocardiography. Pathological characteristics were evaluated through Masson's trichrome staining and wheat germ agglutinin (WGA) staining, revealing pathological features related to DbCM. Therefore, we provide a robust and versatile method for establishing a nongenetic murine model of DbCM.
Insights
This study presents a new mouse model for diabetic cardiomyopathy (DbCM) using a high-fat diet and streptozotocin. This model effectively mimics human T2DM progression and cardiac dysfunction for research.
Area of Science:
- Cardiovascular Biology
- Metabolic Diseases
- Animal Models
Background:
- Diabetic cardiomyopathy (DbCM) is a major complication of type 2 diabetes mellitus (T2DM), but its underlying mechanisms are not fully understood.
- T2DM-related myocardial toxicity involves lipotoxicity, glucotoxicity, oxidative stress, and impaired cardiac efficiency.
- Murine models are valuable for studying T2DM due to their accessibility and cost-effectiveness.
Purpose of the Study:
- To develop and validate a novel, nongenetic murine model that accurately replicates the progressive pathophysiology of human diabetic cardiomyopathy.
- To establish a reproducible method for inducing T2DM and associated cardiac dysfunction in mice.
Main Methods:
- Wild-type C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks, followed by streptozotocin (STZ) injections for 12 weeks.
- Insulin resistance and secretion were assessed via oral glucose tolerance tests and serum insulin measurements.
- Cardiac structure and function were evaluated using transthoracic echocardiography; pathological changes were analyzed with Masson's trichrome and WGA staining.
Main Results:
- The HFD and STZ combination successfully induced T2DM hallmarks, including insulin resistance and impaired insulin secretion.
- Echocardiography revealed significant alterations in cardiac structure and function consistent with DbCM.
- Histological analysis confirmed DbCM-related pathological changes, such as fibrosis and hypertrophy.
Conclusions:
- A robust and versatile nongenetic murine model for studying diabetic cardiomyopathy has been established.
- This model provides a valuable platform for investigating T2DM-induced cardiac pathophysiology and for testing therapeutic interventions.
