Imaging beta-cell death with a near-infrared probe.
Evidence exists for an essential role of beta-cell apoptosis in the pathology of type 1 and type 2 diabetes. Current methods for diabetes-associated apoptosis detection, however, suffer the drawbacks of relying on in situ-based strategies. In this study, we attempted to measure, both in vitro and ex vivo, levels of beta-cell apoptosis in diabetic mice using Cy5.5-labeled annexin V. We used streptozotocin-treated BALB/c mice and NOD mice of different ages as models of type 1 diabetes and db/db mice as a model of type 2 diabetes. With annexin V Cy5.5, we established differences in levels of apoptosis between diabetic and control animals. Intravenously administered annexin V Cy5.5 accumulated in pancreata of diabetic mice but not in nondiabetic controls. Furthermore, its localization was specific to apoptotic events within diabetic islets; its selectivity was supported by transferase-mediated dUTP nick-end labeling staining. Because annexin V defines an early marker of apoptosis and the developed probe is suitable for in vivo administration, it may provide a promising tool for real-time identification in intact animals of the earliest stages of diabetes-associated beta-cell death and for tracing the events that characterize the pathology of the disease.
Medarova
Zdravka
Z
MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129, USA.
Bonner-Weir
Susan
S
Lipes
Myra
M
Moore
Anna
A
D000818:Animals; D017304:Annexin A5; D017209:Apoptosis / Q000502:physiology*; D002232:Carbocyanines; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology; D007259:Infrared Rays; D007515:Islets of Langerhans / Q000473:pathology* / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD
D017304:Annexin A5; C098793:CY5.5 cyanine dye; D002232:Carbocyanines