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Neo-Islet Formation in Liver of Diabetic Mice by Helper-dependent Adenoviral Vector-Mediated Gene Transfer
Published on: October 10, 2012
Repression of the Notch pathway prevents liver damage in streptozotocin-induced diabetic mice
Eda Acikgoz1, Huseyin Aktug, Gurkan Yigitturk
11Yuzuncu Yil University, Faculty of Medicine, Department of Histology and Embryology, Van, Turkey. 2Ege University, Faculty of Medicine, Department of Histology and Embryology, Izmir, Turkey.. acikgozedaa@gmail.com.
Introduction:
Sunitinib is an oral inhibitor of vascular endothelial growth factor that is used to treat a variety of cancer. There are limited data regarding the effect of sunitinib on diabetes. In the liver, Notch signaling plays an important role in liver tissue development and homeostasis and its dysfunction is associated with liver pathol-ogies. The aim of the present study is to investigate the effects of sunitinib on streptozotocin (STZ)-induced diabetic liver in mice models.
Material And Methods:
An experimental diabetes mellitus (DM) model was created in 28 male CD-1 mice. Twenty-eight male CD-1 mice divided in four groups (n = 7 each) were used; control mice (C), control mice treated with sunitinib (C + S), diabetic mice (DM), and diabetic mice treated with sunitinib (DM + S) for four weeks. The histopathological changes in the liver were examined by histochemistry and immunohistochemistry. Immunoreactivity of Notch1, Jagged1, DLL-1 and VEGF were evaluated in control and diabetic mice after sunitinib treatment.
Results:
The significant morphological changes in the liver were mostly seen in hepatocytes that were hyper-trophied in the DM mice, with an increased amount of eosinophilic granules; moreover, some hepatocytes contained empty vacuole-like structures. The livers of the DM mice revealed increased deposition of collagen fibers. After sunitinib treatment the hepatocytes and hepatic lobules had almost similar morphology to control mice. The immunoreactivities of Notch1, Jagged1, DLL-1 and VEGF in hepatocytes were significantly lower in the DM group when compared with the C, DM + S and C + S group treated with sunitinib.
Conclusions:
These results suggest that sunitinib effectively protects the liver from diabetes-induced damage through the inhibition of the Notch pathway.
Insights
Sunitinib treatment protected against liver damage in diabetic mice by inhibiting the Notch pathway. This cancer drug shows promise for managing diabetes-related liver complications.
Area of Science:
- Hepatology
- Endocrinology
- Pharmacology
Background:
- Sunitinib, a vascular endothelial growth factor inhibitor, is used in cancer treatment.
- Limited data exist on sunitinib's effects on diabetes.
- Notch signaling is crucial for liver homeostasis; its dysfunction contributes to liver pathologies.
Purpose of the Study:
- To investigate the effects of sunitinib on streptozotocin (STZ)-induced diabetic liver in mice.
- To evaluate sunitinib's impact on Notch signaling and VEGF in diabetic livers.
Main Methods:
- A mouse model of diabetes mellitus (DM) was established using STZ.
- Mice were divided into four groups: control, control + sunitinib, diabetic, and diabetic + sunitinib.
- Liver histopathology, collagen deposition, and immunoreactivity of Notch1, Jagged1, DLL-1, and VEGF were assessed.
Main Results:
- Diabetic mice exhibited hepatocyte hypertrophy, increased eosinophilic granules, vacuole-like structures, and collagen deposition.
- Sunitinib treatment restored liver morphology closer to control levels.
- Immunoreactivity for Notch1, Jagged1, DLL-1, and VEGF was significantly reduced in diabetic mice but normalized with sunitinib treatment.
Conclusions:
- Sunitinib effectively protects the liver from diabetes-induced damage.
- The protective effect is mediated through the inhibition of the Notch pathway.
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