Very-low-dose streptozotocin induces diabetes in insulin promoter-mB7-1 transgenic mice.
Diabetes
; 44(7): 816-23, 1995 Jul.
Article
en En
| MEDLINE
| ID: mdl-7540575
ABSTRACT
Transgenic mice that express mouse B7-1 (mB7-1, recently designated CD80) on their pancreatic beta-cells maintain normal islet architecture, have normal pancreatic insulin content, and only rarely spontaneously develop insulitis and diabetes. Nevertheless, these mice display an extreme sensitivity to streptozotocin (STZ)-induced diabetes. Female mice were administered two STZ doses intraperitoneally, 20 and 40 mg/kg body wt, each for five consecutive days. Nontransgenic but otherwise syngeneic mice responded to the STZ with a moderate diminution in pancreatic insulin content but not with persistent glycosuria. In striking contrast, STZ administered to transgenic mice resulted in a severe diminution of pancreatic insulin content and in diabetes. Notably, the lower STZ dose resulted in diabetes only after a prolonged (26- to 100-day) latency. STZ-induced diabetes appears to be T-cell dependent, since treatment with T-cell-depleting (and in particular CD8+ subset-depleting) antibodies ameliorated the response. Anti-mB7-1 monoclonal antibody administration also prevented STZ-induced diabetes. Thus, unmasked mB7-1 is a required component in the pathway resulting in beta-cell killing. Immunohistological analysis revealed that early after STZ administration, both mB7-1 transgenic and nontransgenic mice developed insulitis. While this insulitis resolved in the nontransgenic mice, the islet-infiltrating CD4+ and CD8+ T-cells in the transgenic mice were associated with complete beta-cell destruction. These data suggest that STZ-induced diabetes in mB7-1 transgenic mice is an immune-mediated process with distinct potential advantages over existing insulin-dependent diabetes models.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Islotes Pancreáticos
/
Regiones Promotoras Genéticas
/
Estreptozocina
/
Antígeno B7-1
/
Diabetes Mellitus Experimental
/
Insulina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Diabetes
Año:
1995
Tipo del documento:
Article
País de afiliación:
Estados Unidos