Normal Mice the Immune Response to Preproinsulin in Expression of Preproinsulin-2 Gene Shapes
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Specific co-ordinated regulation of PC3 and PC2 gene expression with that of preproinsulin in insulin-producing beta TC3 cells.
Short-term (less than 2 h) glucose stimulation of isolated pancreatic islets specifically increases the biosynthesis of proinsulin and its converting enzymes PC2 and PC3 at the translation level. To determine whether gene expression of PC2 and PC3 was also regulated by longer-term (more than 6 h) glucose stimulation along with that of preproinsulin, studies were performed with the beta TC3 insu...
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Immunization against insulin, insulin B chain, or B chain peptide B(9-23) (preproinsulin peptide II(33-47)) prevents diabetes in the nonobese diabetic (NOD) mouse. Whether or not peptide II(33-47) is the only proinsulin determinant recognized by CD4 T cells remains unclear. Using two peptide libraries spanning the entire sequence of preproinsulin I and preproinsulin II, respectively, we identif...
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Leptin inhibits insulin secretion and preproinsulin gene expression in pancreatic beta-cells, but signal transduction pathways and molecular mechanisms underlying this effect are poorly characterized. In this study, we analyzed leptin-mediated signal transduction and preproinsulin gene regulation at the molecular level in pancreatic beta-cells. Leptin stimulation led to janus kinase (JAK)2-depe...
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OBJECTIVE RIP-B7.1 mice expressing the costimulator molecule B7.1 (CD80) on pancreatic beta-cells are a well established model to characterize preproinsulin-specific CD8 T-cell responses and experimental autoimmune diabetes (EAD). Different immunization strategies could prime preproinsulin-specific CD8 T-cells in wild-type C57BL/6 (B6) mice, but did not induce diabetes. We tested whether alteri...
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Proinsulin is a key Ag in type 1 diabetes, but the mechanisms regulating proinsulin immune tolerance are unknown. We have shown that preproinsulin-2 gene-deficient mice (proins-2(-/-)) are intolerant to proinsulin-2. In this study, we analyzed the mechanisms underlying T cell-mediated tolerance to proinsulin-2 in 129/Sv nonautoimmune mice. The expression of one proinsulin-2 allele, whatever its...
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تاریخ انتشار 2003