Related Experiment Video
Updated: Aug 14, 2026
Development and Validation of a Methodology for Establishing Obese Rat Models with Typical Fatty Pancreas
Published on: November 11, 2025
Insulin status differentially affects energy transduction in cardiac mitochondria from male and female rats
Framroze R Billimoria1, Surendra S Katyare, Samir P Patel
1Department of Biochemistry, Terna Medical College, Nerul, Navi Mumbai, India.
Insights
Diabetic women face higher heart disease risks. This study reveals sex-specific mitochondrial dysfunction in diabetes, with insulin treatment showing differential effects in male and female rats, potentially explaining increased female cardiomyopathy incidence.
Area of Science:
- Biochemistry
- Cardiology
- Endocrinology
Background:
- Diabetic patients exhibit higher rates of coronary heart disease (CHD), congestive heart failure (CHF), and myocardial infarction compared to non-diabetic individuals.
- These cardiovascular complications are notably more prevalent in women than in men.
Purpose of the Study:
- To investigate the role of mitochondrial energy transduction in the increased incidence of cardiovascular diseases in diabetic women.
- To examine the effects of insulin treatment on mitochondrial function in a rat model of diabetes.
Main Methods:
- Utilized streptozotocin (STZ)-induced diabetic male and female rats to model diabetic cardiomyopathy.
- Assessed mitochondrial energy metabolism, including respiration rates, cytochrome content, and dehydrogenase activities.
- Evaluated the impact of two different insulin treatment regimens.
Main Results:
- Diabetes decreased body and heart weights in both sexes; insulin partially restored these in females.
- Mitochondrial respiration and substrate oxidation were impaired in diabetic rats, with insulin showing differential effects between sexes.
- Insulin-induced hyper-stimulation of respiration in females may increase reactive oxygen species production, contributing to cardiovascular risk.
Conclusions:
- Sex-specific differences in mitochondrial energy metabolism and response to insulin treatment in STZ-diabetic rats may underlie the higher incidence of diabetic cardiomyopathy in females.
- Advanced glycosylation end products may further exacerbate cardiovascular risk in diabetic individuals.
Aim:
The incidence of coronary heart diseases (CHD), congestive heart failure (CHF) and myocardial infarction is higher in diabetic patients than in non-diabetic groups, with these incidences being more in women than in the men. Hence, we examined involvement of mitochondrial energy transduction functions.
Methods:
Mitochondrial energy metabolism in cardiomyopathy was studied using streptozotocin (STZ)-diabetic male and female rats as the model system. Effects of insulin treatment were also evaluated.
Results:
The body and heart weights decreased in both male and female diabetic rats. Insulin treatments resulted in significant increase in the body and heart weights in the female rats. Mitochondrial respiration rates with all the substrates tested decreased in diabetic condition in both males and females. Treatment with two dose-regimens of insulin had differential restorative effect on mitochondrial substrate oxidation in the males but caused hyper-stimulation in the females. Diabetic state brought about 19% decrease in the cytochrome aa(3) content in the female rats. Treatment with 0.6 units of insulin significantly increased the cytochrome contents in general in both the sexes whereas higher dose (1.0 unit) caused decrease in the cytochromes content in the females. Diabetic state resulted in decreased dehydrogenases activities; insulin treatments had differential effect on the dehydrogenase activity in the males and the females. The results suggest that insulin treatment-induced hyper-stimulation of respiration in female rats may lead to increased production of reactive oxygen species. Besides, increased formation of advanced glycosylated end products may further lead to increased risk of CHF and CHD.
Conclusions:
The results suggest that differential effects of STZ-diabetes and insulin treatments in the female rats than in males may be the underlying cause for increased incidence of diabetic cardiomyopathies in the females.
