title: Insulin therapy improves islet functions by restoring pancreatic vasculature in high-fat diet-fed streptozotocin-diabetic rats.
abstract: BACKGROUND
  In a previous study, we showed early insulin therapy could improve β-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.
  
  
  METHODS
  Diabetes was induced in rats by a combination of low dose streptozotocin (STZ; 40 mg/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.
  
  
  RESULTS
  Treatment with NPH improved insulin secretion from β-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.
  
  
  CONCLUSIONS
  The 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.
authors.forename: Huimin
authors.initials: H
authors.lastname: Gu
authors.forename: Xuan
authors.initials: X
authors.lastname: Xia
authors.forename: Zonglan
authors.initials: Z
authors.lastname: Chen
authors.forename: Hua
authors.initials: H
authors.lastname: Liang
authors.forename: Jinhua
authors.initials: J
authors.lastname: Yan
authors.forename: Fen
authors.initials: F
authors.lastname: Xu
authors.forename: Jianping
authors.initials: J
authors.lastname: Weng
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D059305:Diet, High-Fat / Q000009:adverse effects; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007336:Insulin, Isophane / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007515:Islets of Langerhans / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D007336:Insulin, Isophane; D040301:Vascular Endothelial Growth Factor Receptor-2