title: Insulin treatment restores islet microvascular vasomotion function in diabetic mice.
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.
  
  
  CONCLUSIONS
  The results suggest that the functional status of PIM vasomotion is impaired in diabetic mice but can be restored by insulin.
authors.affiliation: Key Laboratory of Microcirculation, Institute of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Key Laboratory of Microcirculation, Institute of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Microcirculation, Institute of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Li
authors.affiliation: Laboratory of Electron Microscopy, Ultrastructural Pathology Center, Peking University First Hospital, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Microcirculation, Institute of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Key Laboratory of Microcirculation, Institute of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Bingwei
authors.initials: B
authors.lastname: Li
authors.affiliation: Key Laboratory of Microcirculation, Institute of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
authors.affiliation: Key Laboratory of Microcirculation, Institute of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Microcirculation, Institute of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Xiu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects* / Q000235:genetics; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects* / Q000235:genetics; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014666:Vasomotor System / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D007328:Insulin; D042461:Vascular Endothelial Growth Factor A; D013311:Streptozocin
keywords: diabetes; islet endothelial cell; ultrastructure; vasomotion; 糖尿病; 胰岛内皮细胞; 自律运动; 超微结构