title: Molecular pathways altered by insulin b9-23 immunization.
abstract: Type 1 diabetes (T1D) in the nonobese diabetic (NOD) mouse can be delayed by administration of insulin or specific insulin peptides. To better understand how insulin treatment delays diabetes development, NOD mice treated with an insulin peptide (B9-23) were compared with age-matched NOD and NOD congenic mice for gene expression changes in spleen using cDNA microarray. Fifty genes were identified that were significantly altered by B9-23 treatment. Thirty-three of these genes are downregulated by the treatment while they are upregulated during the natural disease progression in NOD from immature (3-4 weeks) to mature (10 weeks) stages. Taken together, our data suggest that the B9-23 treatment, like the protective genes in NOD congenic strains, reduces pro-inflammatory activation of lymphocytes that normally occurs in NOD mice. Furthermore, our studies discovered two genes (Irf4 and Tra1) with increased expression in B9-23-treated mice that promote the Th2 response, providing a molecular basis for the B9-23-protective therapy.
authors.affiliation: CBGM, Medical College of Georgia, 1120 15th Street, CA-4124, Augusta, GA 30912, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Eckenrode
authors.forename: Qing-Guo
authors.initials: QG
authors.lastname: Ruan
authors.forename: Christin D
authors.initials: CD
authors.lastname: Collins
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Richard A
authors.initials: RA
authors.lastname: McIndoe
authors.forename: Andrew
authors.initials: A
authors.lastname: Muir
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007114:Immunization; D007328:Insulin / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D020297:Mice, Congenic; D016688:Mice, Inbred NOD; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D007328:Insulin; D010446:Peptide Fragments