Spatial distribution and temporal onset of NF-kB activation and inducible nitric oxide synthase within pancreatic islets in the pre-diabetic stage of genetic, diabetic-prone BB rats: attenuation by drug intervention decreases inflammatory cell infiltration and incidence of diabetes. Inflamm Res 2004 Jan;53(1):22-30
Date
03/17/2004Pubmed ID
15021977DOI
10.1007/s00011-003-1223-3Scopus ID
2-s2.0-1642576221 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
OBJECTIVE AND DESIGN: To document in vivo immunolocalization and activation of nuclear factor-kappaB (NF-kappaB) and inducible nitric oxide synthase (iNOS) expression in prediabetic stages of diabetes mellitus.
MATERIAL OR SUBJECTS: Genetic, diabetic-prone or diabetic-resistant BB rats (total = 189).
TREATMENT: Various doses of an oral dithiocarbamate derivative, NOX-700, or cyclosporine (2.5 mg/kg) starting at 30 or 60 days of age.
METHODS: Immunohistochemistry, electrophoretic mobility shift assays, plasma glucose.
RESULTS: NF-kappaB and iNOS was increased in pancreas of hyperglycemic, diabetic-prone rats but not normoglycemic, diabetic-resistant rats. Immunostaining for NF-kappaB and iNOS was largely confined to islets and occurred in diabetic-prone rats prior to overt hyperglycemia. NOX-700 decreased cell infiltration, delayed the onset of disease and decreased the incidence of hyperglycemia to levels achieved by immunosuppressant therapy. NOX-700 also decreased the intensity of immunoreactive NF-kappaB and iNOS within pancreatic islets.
CONCLUSIONS: These studies support a role of NF-kB and iNOS in diabetogenesis in vivo.
Author List
Pieper CM, Roza AM, Henderson JD Jr, Zhu YR, Lai CSMESH terms used to index this publication - Major topics in bold
AnimalsDiabetes Mellitus, Type 1
Drug Administration Schedule
Electrophoresis
Genetic Predisposition to Disease
Hyperglycemia
Immunohistochemistry
Islets of Langerhans
Male
NF-kappa B
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Pancreas
Prediabetic State
Rats
Rats, Inbred BB
Thiocarbamates
Time Factors
Tissue Distribution
