PT  - JOURNAL ARTICLE
AU  - Watanabe, Ayahisa
AU  - Nishijima, Ken-ichi
AU  - Zhao, Songji
AU  - Zhao, Yan
AU  - Tanaka, Yoshikazu
AU  - Takemoto, Hiroshi
AU  - Strauss, H. William
AU  - Blankenberg, Francis G.
AU  - Tamaki, Nagara
AU  - Kuge, Yuji
TI  - Quantitative Determination of Apoptosis of Pancreatic β-Cells in a Murine Model of Type 1 Diabetes Mellitus
AID  - 10.2967/jnumed.111.102459
DP  - 2012 Oct 01
TA  - Journal of Nuclear Medicine
PG  - 1585--1591
VI  - 53
IP  - 10
4099  - http://jnm.snmjournals.org/content/53/10/1585.short
4100  - http://jnm.snmjournals.org/content/53/10/1585.full
SO  - J Nucl Med2012 Oct 01; 53
AB  - 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 99mTc-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 99mTc-annexin A5 and sacrificed 6 h later for autoradiography, and the regional 99mTc-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 99mTc-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 × 106/mm2/kg). The level of apoptotic cells in pancreatic islets was expressed as the number of TUNEL-positive cells per area of pancreatic islets (cells/mm2). Results: The 99mTc-annexin A5 accumulation level was significantly higher (2.5 ± 0.7 vs. 0.7 ± 0.1 %ID × 106/mm2/kg, P < 0.05) and the number of TUNEL-positive cells was significantly higher (1,170 ± 535 vs. 5 ± 6 cells/mm2, P < 0.05) in the pancreatic islets of the streptozotocin-treated mice than in those of the vehicle-treated mice. The 99mTc-annexin A5 accumulation level was significantly higher (1.1 ± 0.4 vs. 0.5 ± 0.1 %ID × 106/mm2/kg, P < 0.05) and the number of TUNEL-positive cells was significantly higher (152 ± 82 vs. 4 ± 9 cells/mm2, 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 99mTc-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). Conclusion: There is significant islet cell apoptosis with 99mTc-annexin A5 accumulation in the pancreas of both streptozotocin and NOD mice.