Development of an Early-Stage Diabetic Cardiomyopathy Rat Model with Early Myocardial Remodeling Induced by HFHF Diet and Low-Dose Streptozotocin
9 affiliations
- 1Doctoral Program in Medical Sciences, Faculty of Medicine, Universitas Indonesia/National Cardiovascular Center Harapan Kita, Jakarta, Indonesia
- 2Doctoral Program in Medical Sciences/Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Indonesia/National Cardiovascular Center Harapan Kita, Jakarta, Indonesia
- 3Doctoral Program in Medical Sciences/Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo General Hospital Jakarta, Indonesia
- 4Department of Community Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
- 5Department of Pharmacology-Toxicology, Faculty of Pharmacy, Universitas Indonesia, Jakarta, Indonesia
- 6Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga/Dr. Soetomo General Academic Hospital – Universitas Airlangga Hospital, Surabaya, Indonesia
- 7Division of Surgery and Radiology, School of Veterinary Medicine and Biomedical Sciences, IPB University, Bogor, Indonesia
- 8Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- 9Doctoral Program in Medical Sciences/Department of Anatomical Pathology/Animal Research Facility, IMERI, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
Abstract
Background: Diabetic Cardiomyopathy (DCM) is defined as structural and functional abnormalities of the myocardium occurring in individuals with Diabetes Mellitus (DM) in the absence of other conventional cardiovascular risk factors. Establishing a reliable early-stage DCM model is essential for mechanistic studies and therapeutic evaluation. This study aimed to characterize an early-stage DCM model in male Sprague–Dawley rats using a High-Fat High-Fructose (HFHF) diet combined with low-dose Streptozotocin (STZ).
Methods: Twelve male Sprague–Dawley rats (7–8 weeks, 200–250 g) were randomly assigned to three groups (n=4/group): control, HFHF + STZ 25 mg/kg, and HFHF + STZ 40 mg/kg. Rats received an HFHF diet for 12 weeks, followed by intraperitoneal STZ induction. Fasting blood glucose, lipid profile, cardiac echocardiography, serum N-Terminal pro-B-type Natriuretic Peptide (NT-proBNP), and myocardial histopathology were assessed. Data were analyzed using ANOVA or Kruskal–Wallis as appropriate.
Results: Both STZ doses induced persistent hyperglycemia without significant body-weight changes, consistent with a DCM metabolic phenotype. NT-proBNP levels were significantly elevated in both STZ groups compared with controls (p<0.05), indicating early myocardial stress despite preserved systolic and diastolic function on echocardiography. Histopathological evaluation showed increased inflammatory cell infiltration and progressive fibrosis in the HFHF+STZ groups, with a graded pattern across STZ doses.
Conclusions: The combination of an HFHF diet and low-dose STZ reproduced an early-stage DCM model characterized by persistent hyperglycemia, elevated NT-proBNP, and early myocardial remodeling while cardiac function remains preserved. This model reflects early DCM and is suitable for mechanistic studies and for testing therapies aimed at preventing progression to advanced myocardial dysfunction.
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BibTeX
@article{atmojo2026development,
title = {{Development of an Early-Stage Diabetic Cardiomyopathy Rat Model with Early Myocardial Remodeling Induced by HFHF Diet and Low-Dose Streptozotocin}},
author = {Susetyo Atmojo and Bambang Budi Siswanto and Nurjati Chairani Siregar and Aria Kekalih and Fadlina Chany Saputri and Budi Susetyo Pikir and Deni Noviana and Khanisyah Erza Gumilar and Puspita Eka Wuyung},
journal = {Majalah Kardiologi Indonesia},
year = {2026},
month = oct,
doi = {10.30701/ijc.2194},
url = {https://doi.org/10.30701/ijc.2194},
note = {CC BY},
}
RIS
TY - JOUR
TI - Development of an Early-Stage Diabetic Cardiomyopathy Rat Model with Early Myocardial Remodeling Induced by HFHF Diet and Low-Dose Streptozotocin
AU - Susetyo Atmojo
AU - Bambang Budi Siswanto
AU - Nurjati Chairani Siregar
AU - Aria Kekalih
AU - Fadlina Chany Saputri
AU - Budi Susetyo Pikir
AU - Deni Noviana
AU - Khanisyah Erza Gumilar
AU - Puspita Eka Wuyung
PY - 2026
DA - 2026/10/25
JO - Majalah Kardiologi Indonesia
DO - 10.30701/ijc.2194
UR - https://doi.org/10.30701/ijc.2194
AB - Background: Diabetic Cardiomyopathy (DCM) is defined as structural and functional abnormalities of the myocardium occurring in individuals with Diabetes Mellitus (DM) in the absence of other conventional cardiovascular risk factors. Establishing a reliable early-stage DCM model is essential for mechanistic studies and therapeutic evaluation. This study aimed to characterize an early-stage DCM model in male Sprague–Dawley rats using a High-Fat High-Fructose (HFHF) diet combined with low-dose Streptozotocin (STZ). Methods: Twelve male Sprague–Dawley rats (7–8 weeks, 200–250 g) were randomly assigned to three groups (n=4/group): control, HFHF + STZ 25 mg/kg, and HFHF + STZ 40 mg/kg. Rats received an HFHF diet for 12 weeks, followed by intraperitoneal STZ induction. Fasting blood glucose, lipid profile, cardiac echocardiography, serum N-Terminal pro-B-type Natriuretic Peptide (NT-proBNP), and myocardial histopathology were assessed. Data were analyzed using ANOVA or Kruskal–Wallis as appropriate. Results: Both STZ doses induced persistent hyperglycemia without significant body-weight changes, consistent with a DCM metabolic phenotype. NT-proBNP levels were significantly elevated in both STZ groups compared with controls (p<0.05), indicating early myocardial stress despite preserved systolic and diastolic function on echocardiography. Histopathological evaluation showed increased inflammatory cell infiltration and progressive fibrosis in the HFHF+STZ groups, with a graded pattern across STZ doses. Conclusions: The combination of an HFHF diet and low-dose STZ reproduced an early-stage DCM model characterized by persistent hyperglycemia, elevated NT-proBNP, and early myocardial remodeling while cardiac function remains preserved. This model reflects early DCM and is suitable for mechanistic studies and for testing therapies aimed at preventing progression to advanced myocardial dysfunction.
SN - 0126-3773
SN - 2620-4762
ER -