Related Experiment Video
Updated: Oct 9, 2025
A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes
Published on: February 17, 2023
Therapeutic Potential of Sunitinib in Ameliorating Endothelial Dysfunction in Type 2 Diabetic Rats
Ali Mahdi1, Tong Jiao1, Yahor Tratsiakovich1
1Unit of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Introduction:
Sunitinib, a multi-targeted tyrosine kinase receptor inhibitor used to treat renal-cell carcinoma and gastrointestinal stromal tumor, was recently shown to have a beneficial effect on metabolism in type 2 diabetes (T2D). Endothelial dysfunction is a key factor behind macro- and microvascular complications in T2D. The effect of sunitinib on endothelial function in T2D remains, however, unclear. We therefore tested the hypothesis that sunitinib ameliorates endothelial dysfunction in T2D.
Methods:
Sunitinib (2 mg/kg/day, by gavage) was administered to T2D Goto-Kakizaki (GK) rats for 6 weeks, while water was given to GK and Wistar rats as controls. Hemodynamic, inflammatory, and metabolic parameters as well as endothelial function were measured.
Results:
Systolic, mean arterial blood pressures, plasma tumor necrosis factor α levels, kidney weight to body weight (BW) ratio, and glucose levels were higher, while BW was lower in GK rats than in Wistar rats. Six-week treatment with sunitinib in GK rats did not affect these parameters but suppressed the increase in glucose levels. Endothelium-dependent relaxations were reduced in both aortas and mesenteric arteries isolated from GK as compared to Wistar rats, which was markedly reversed in both types of arteries from GK rats treated with sunitinib.
Conclusions:
This study demonstrates that sunitinib has a glucose-lowering effect and ameliorates endothelial dysfunction in both conduit and resistance arteries of GK rats.
Insights
Sunitinib treatment improved glucose levels and reversed endothelial dysfunction in diabetic rats, suggesting potential benefits for type 2 diabetes complications.
Area of Science:
- Pharmacology
- Diabetology
- Cardiovascular Research
Background:
- Sunitinib, a tyrosine kinase inhibitor, shows metabolic benefits in type 2 diabetes (T2D).
- Endothelial dysfunction is a major contributor to T2D vascular complications.
- The impact of sunitinib on T2D endothelial function requires further investigation.
Purpose of the Study:
- To evaluate the effect of sunitinib on endothelial function in a rat model of type 2 diabetes.
- To test the hypothesis that sunitinib ameliorates endothelial dysfunction in T2D.
Main Methods:
- Administration of sunitinib (2 mg/kg/day) to Goto-Kakizaki (GK) diabetic rats for 6 weeks.
- Measurement of hemodynamic, inflammatory, metabolic parameters, and endothelial function.
- Comparison between treated GK rats, untreated GK rats, and Wistar controls.
Main Results:
- Sunitinib treatment suppressed the rise in glucose levels in GK rats.
- Endothelium-dependent relaxations were impaired in GK rats compared to Wistar rats.
- Sunitinib treatment markedly reversed the impaired relaxations in both conduit and resistance arteries of GK rats.
Conclusions:
- Sunitinib demonstrates a glucose-lowering effect in diabetic rats.
- Sunitinib ameliorates endothelial dysfunction in both conduit and resistance arteries of GK rats.
- These findings suggest sunitinib's potential therapeutic role in managing T2D vascular complications.
