Mingming Liu1, Xiaoyan Zhang1, Ailing Li1, Xu Zhang2, Bing Wang1, Bingwei Li1, Shuying Liu1, Hongwei Li1, Ruijuan Xiu1. 1. Key Laboratory of Microcirculation, Institute of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 2. Laboratory of Electron Microscopy, Ultrastructural Pathology Center, Peking University First Hospital, Beijing, China.
Abstract
BACKGROUND: The microcirculation plays an important role in the pathogenesis of diabetes and its complications. We hypothesized that pancreatic islet microvascular (PIM) vasomotion, as a parameter of pancreatic islet microcirculation function, is abnormal in diabetic mice and that insulin treatment may reverse this dysfunction. METHODS: Mice were randomly assigned to non-diabetic control, untreated diabetic, and insulin-treated diabetic groups (n = 6 in each group). Separate groups of streptozotocin (STZ)-induced diabetic and high-fat diet-fed mice were used as a model of hyperglycemia. Insulin-treated diabetic mice were treated with 1-1.5 IU/day insulin for 1 week. Laser Doppler monitors were used to evaluate PIM vasomotion. Morphological and ultrastructural changes in islet endothelial cells were determined by immunohistochemistry and transmission electron microscopy. Glucagon, insulin, vascular endothelial growth factor (VEGF)-A, and platelet endothelial cell adhesion molecule (PECAM-1) expression was determined by immunohistochemistry and Western blotting. RESULTS: In both untreated diabetic groups, the pancreatic islet microcirculation was unable to regulate PIM vasomotion. The rhythm of vasomotion was irregular, and the average blood perfusion, amplitude, frequency, and relative velocity of vasomotion were significantly lower than in non-diabetic controls. Insulin treatment restored the functional status of PIM vasomotion. In islet endothelial cells from both untreated diabetic groups, the mitochondria were swollen with disarrangement of the cristae, and the distribution of PECAM-1 was discontinuous. Insulin treatment significantly increased the reduced expression of PECAM-1 in both untreated diabetic groups and VEGF-A expression in untreated STZ-diabetic mice. CONCLUSION: The results suggest that the functional status of PIM vasomotion is impaired in diabetic mice but can be restored by insulin.
BACKGROUND: The microcirculation plays an important role in the pathogenesis of diabetes and its complications. We hypothesized that pancreatic islet microvascular (PIM) vasomotion, as a parameter of pancreatic islet microcirculation function, is abnormal in diabeticmice and that insulin treatment may reverse this dysfunction. METHODS:Mice were randomly assigned to non-diabetic control, untreated diabetic, and insulin-treated diabetic groups (n = 6 in each group). Separate groups of streptozotocin (STZ)-induced diabetic and high-fat diet-fed mice were used as a model of hyperglycemia. Insulin-treated diabeticmice were treated with 1-1.5 IU/day insulin for 1 week. Laser Doppler monitors were used to evaluate PIM vasomotion. Morphological and ultrastructural changes in islet endothelial cells were determined by immunohistochemistry and transmission electron microscopy. Glucagon, insulin, vascular endothelial growth factor (VEGF)-A, and platelet endothelial cell adhesion molecule (PECAM-1) expression was determined by immunohistochemistry and Western blotting. RESULTS: In both untreated diabetic groups, the pancreatic islet microcirculation was unable to regulate PIM vasomotion. The rhythm of vasomotion was irregular, and the average blood perfusion, amplitude, frequency, and relative velocity of vasomotion were significantly lower than in non-diabetic controls. Insulin treatment restored the functional status of PIM vasomotion. In islet endothelial cells from both untreated diabetic groups, the mitochondria were swollen with disarrangement of the cristae, and the distribution of PECAM-1 was discontinuous. Insulin treatment significantly increased the reduced expression of PECAM-1 in both untreated diabetic groups and VEGF-A expression in untreated STZ-diabeticmice. CONCLUSION: The results suggest that the functional status of PIM vasomotion is impaired in diabeticmice but can be restored by insulin.