Insulin therapy improves islet functions by restoring pancreatic vasculature in high-fat diet-fed streptozotocin-diabetic rats

BackgroundIn a previous study, we showed early insulin therapy could improve -cell function in type 2 diabetic patients. However, the molecular mechanism was not clear. In the present study, we addressed this question by analyzing the pancreatic microvasculature in diabetic rats after insulin treatment. MethodsDiabetes was induced in rats by a combination of low dose streptozotocin (STZ; 40mg/kg) and feeding of a high-fat diet. After the induction of diabetes, rats were treated with neutral protamine Hagedorn insulin (NPH; 6-8 U/day, s.c.) for 3 weeks. Three days after the end of treatment, rats were subjected to an intraperitoneal glucose tolerance test (IPGTT). The pancreatic microvasculature and the amount and size of the islets were evaluated by immunohistochemistry. Western blot analysis was used to determine levels of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGF-R2) protein. ResultsTreatment with NPH improved insulin secretion from -cells during the IPGTT and increased pancreatic islet size. The density of the microvasculature in the pancreas was determined by quantification of CD31, a marker of endothelial cells. Insulin treatment increased CD31 protein levels, as well as the expression of VEGF and VEGFR2. ConclusionsThe results suggest that insulin treatment improves islet recovery by increasing angiogenesis in the pancreas. The mechanism is related to the induction of VEGF and VEGFR2 expression in diabetic rats. ?? ????????,???????????????2?????????????,??????????????????????2???????????????????????? ????????????(40 mg/kg)????????????????????,???????????(NPH,6-8 U/?,????)??3???????3???????????(IPGTT),???????????????????????????;??western blotting???????????????(vascular endothelial growth factor,VEGF)????2(VEGF-R2)??????? ??NPH???IPGTT?????????????,??????????????????CD31?????????????????????????CD31??????VEGF?VEGF-R2???? ???????????????????????????????????,??????VEGF?VEGF-R2??????