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 CSAuthor
Allan Roza MD Emeritus Professor in the Surgery department at Medical College of WisconsinMESH 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
