Effects of insulin therapy on fracture healing and expression of VEGF in diabetic rats

Abstract

Summary This study was designed to investigate effects of insulin on fracture healing and expression of vascular endothelial growth factor (VEGF) in diabetic rats. Wister rats were randomly divided into diabetic control (n=66), diabetic insulin (=66) and non-diabetic control group (n=66). Diabetes was established by peritoneal injection of alloxan. Tibia fracture was surgically created and was allowed to heal. Radiological and biomechanical examinations were performed on the healing tibia. Immuohistochemistry was used to assess VEGF expression in the healing fracture tissues. Cortical reconstruction of the fracture sites in non-diabetic control and diabetic insulin groups was more rapid than in diabetic control group within 6 weeks of the fracture. Mechanical strength of the affected tibia in the diabetic insulin and non-diabetic control group was superior to diabetic control group. Histological examination of the fracture sites revealed a delay in chondrocyte maturation and hypertrophy in diabetic control group. VEGF expression was widely distributed in fracture sites within the first 4 weeks in control and diabetic insulin treatment group. However VEGF expression in the callus and periosteum in diabetic control group was much less than in diabetic insulin or non-diabetic control group. In conclusion, diabetes delays fracture healing and adversely affects callus formation with a reduced VEGF expression at the fracture sites. Insulin therapy improves fracture healing in diabetes rats, possibly through enhancing VEGF expression in the fractured bones.