XXXX induces intracisternal type A retroviral gene transcription and translation in pancreatic beta cells.

@entity70995 @entity6 @entity28 @entity19 @entity413
C57BL/KsJ (BKs) and CBA/J, but not C57BL/6J (B6) @entity19 are susceptible to the diabetogenic action of the @entity28 gene, " @entity6 " (db). BKs and CBA/J, but not B6 @entity19 , constitutively express intracisternal type A particles (IAP), an endogenous class of retrovirus, in beta cells and in cortical thymocytes. IAP genetic expression in these cell types included production of the group-specific antigen, @entity70995 , as well as higher-molecular mass @entity70995 -related antigens (p114-120). We used islet culture techniques to show that both transcription and translation of IAP genomes in beta cells in enhanced by @entity413 . Maintenance of CBA/J islets for 48 h in 16.5 mM @entity413 -containing medium effected a fivefold induction of IAP protein synthesis in comparison to islets cultured in low- (5.5 mM) @entity413 medium. Analysis of RNA from 16.5 mM @entity413 -cultured islets revealed induction of 7.2 and 5.4 kbp transcripts known to code for @entity70995 and the p114-120 polypeptides, respectively. This induction in CBA/J islets was 10-15-fold on a tissue basis, and 5-7-fold on an RNA basis. @entity413 induction of preproinsulin mRNA levels was also analyzed in the same samples. Islets cultured in 16.5 mM @entity413 showed an eightfold higher level on a tissue basis, and a fourfold increase in terms of total recovered RNA. Comparison of these @entity413 -inducible parameters in islets isolated from the @entity6 -susceptible BKs strain vs. the resistant B6 strain revealed that expression of the group-specific retroviral @entity70995 antigen was limited to BKs beta cells. This inbred strain control of @entity70995 expression was also found in cortical thymocytes, with B6 thymocytes producing a 117 kD component to the exclusion of @entity70995 , while both components were expressed in thymocytes from normal BKs @entity19 . In comparison to normal BKs males, thymocytes from four week-old genetically @entity6 (db/db) BKs males showed no change in labeling of p117, but showed a sharply diminished incorporation into @entity70995 . This suggested that accelerated thymic involution characteristic of db/db @entity19 may entail selective elimination of @entity70995 -producing cells. The possibility that @entity413 -stressed BKs pancreatic beta cells are marked for autoimmune elimination by the elaboration of @entity70995 or other IAP-related proteins is discussed.
