title: Quantitative determination of apoptosis of pancreatic β-cells in a murine model of type 1 diabetes mellitus.
abstract: Type 1 diabetes mellitus is characterized by a significant deficit in pancreatic β-cell mass, presumably caused by β-cell apoptosis. We investigated the incidence of β-cell apoptosis in streptozotocin-treated mice and nonobese diabetic (NOD) mice with (99m)Tc-annexin A5.
  
  
  METHODS
  Vehicle-treated mice, streptozotocin-treated mice, and NOD mice at the ages of 5, 9, 16, and 20 wk (5-8 mice per group) were injected with (99m)Tc-annexin A5 and sacrificed 6 h later for autoradiography, and the regional (99m)Tc-annexin A5 level in the pancreas was evaluated. Pancreatic islets were identified by insulin immunohistochemical staining, and apoptotic cells were determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. The (99m)Tc-annexin A5 level in pancreatic islets was expressed as the percentage injected dose per area of pancreatic islets and normalized by animal body weight (%ID × 10(6)/mm(2)/kg). The level of apoptotic cells in pancreatic islets was expressed as the number of TUNEL-positive cells per area of pancreatic islets (cells/mm(2)).
  
  
  RESULTS
  The (99m)Tc-annexin A5 accumulation level was significantly higher (2.5 ± 0.7 vs. 0.7 ± 0.1 %ID × 10(6)/mm(2)/kg, P < 0.05) and the number of TUNEL-positive cells was significantly higher (1,170 ± 535 vs. 5 ± 6 cells/mm(2), P < 0.05) in the pancreatic islets of the streptozotocin-treated mice than in those of the vehicle-treated mice. The (99m)Tc-annexin A5 accumulation level was significantly higher (1.1 ± 0.4 vs. 0.5 ± 0.1 %ID × 10(6)/mm(2)/kg, P < 0.05) and the number of TUNEL-positive cells was significantly higher (152 ± 82 vs. 4 ± 9 cells/mm(2), P < 0.05) in the pancreatic islets of 16-wk-old NOD mice than in those of 5-wk-old NOD mice. In addition, the level of (99m)Tc-annexin A5 correlated with the number of TUNEL-positive cells in the pancreatic islets of the streptozotocin-treated mice (r = 0.821, P < 0.001) and NOD mice (r = 0.721, P < 0.001).
  
  
  CONCLUSIONS
  There is significant islet cell apoptosis with (99m)Tc-annexin A5 accumulation in the pancreas of both streptozotocin and NOD mice.
authors.affiliation: Department of Radiobiology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Ayahisa
authors.initials: A
authors.lastname: Watanabe
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nishijima
authors.forename: Songji
authors.initials: S
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takemoto
authors.forename: H William
authors.initials: HW
authors.lastname: Strauss
authors.forename: Francis G
authors.initials: FG
authors.lastname: Blankenberg
authors.forename: Nagara
authors.initials: N
authors.lastname: Tamaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D001345:Autoradiography; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D015609:Organotechnetium Compounds
chemical_list: D017304:Annexin A5; D001786:Blood Glucose; D015609:Organotechnetium Compounds