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. 1986 Jan 1;163(1):87–100. doi: 10.1084/jem.163.1.87

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

PMCID: PMC2188002  PMID: 3079815

Abstract

C57BL/KsJ (BKs) and CBA/J, but not C57BL/6J (B6) mice are susceptible to the diabetogenic action of the obesity gene, "diabetes" (db). BKs and CBA/J, but not B6 mice, 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, p73, as well as higher-molecular mass p73-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 glucose. Maintenance of CBA/J islets for 48 h in 16.5 mM glucose-containing medium effected a fivefold induction of IAP protein synthesis in comparison to islets cultured in low- (5.5 mM) glucose medium. Analysis of RNA from 16.5 mM glucose-cultured islets revealed induction of 7.2 and 5.4 kbp transcripts known to code for p73 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. Glucose induction of preproinsulin mRNA levels was also analyzed in the same samples. Islets cultured in 16.5 mM glucose showed an eightfold higher level on a tissue basis, and a fourfold increase in terms of total recovered RNA. Comparison of these glucose-inducible parameters in islets isolated from the diabetes- susceptible BKs strain vs. the resistant B6 strain revealed that expression of the group-specific retroviral p73 antigen was limited to BKs beta cells. This inbred strain control of p73 expression was also found in cortical thymocytes, with B6 thymocytes producing a 117 kD component to the exclusion of p73, while both components were expressed in thymocytes from normal BKs mice. In comparison to normal BKs males, thymocytes from four week-old genetically diabetic (db/db) BKs males showed no change in labeling of p117, but showed a sharply diminished incorporation into p73. This suggested that accelerated thymic involution characteristic of db/db mice may entail selective elimination of p73-producing cells. The possibility that glucose- stressed BKs pancreatic beta cells are marked for autoimmune elimination by the elaboration of p73 or other IAP-related proteins is discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brunstedt J., Chan S. J. Direct effect of glucose on the preproinsulin mRNA level in isolated pancreatic islets. Biochem Biophys Res Commun. 1982 Jun 30;106(4):1383–1389. doi: 10.1016/0006-291x(82)91267-0. [DOI] [PubMed] [Google Scholar]
  2. Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
  3. Collier S. A., Mandel T. E., Carter W. M. Detrimental effect of high medium glucose concentration on subsequent endocrine function of transplanted organ-cultured foetal mouse pancreas. Aust J Exp Biol Med Sci. 1982 Aug;60(Pt 4):437–445. doi: 10.1038/icb.1982.49. [DOI] [PubMed] [Google Scholar]
  4. Dardenne M., Savino W., Gastinel L. N., Nabarra B., Bach J. F. Thymic dysfunction in the mutant diabetic (db/db) mouse. J Immunol. 1983 Mar;130(3):1195–1199. [PubMed] [Google Scholar]
  5. Hanahan D. Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature. 1985 May 9;315(6015):115–122. doi: 10.1038/315115a0. [DOI] [PubMed] [Google Scholar]
  6. Howell S. L., Taylor K. W. The secretion of newly synthesized insulin in vitro. Biochem J. 1967 Mar;102(3):922–927. doi: 10.1042/bj1020922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Irvine W. J. Immunological aspects of diabetes mellitus. Adv Exp Med Biol. 1979;119:147–155. doi: 10.1007/978-1-4615-9110-8_22. [DOI] [PubMed] [Google Scholar]
  8. Kakita K., O'Connell K., Permutt M. A. Pancreatic content of insulins I and II in laboratory rodents. Analysis by immunoelectrophoresis. Diabetes. 1982 Oct;31(10):841–845. doi: 10.2337/diab.31.10.841. [DOI] [PubMed] [Google Scholar]
  9. Kolb H., Kiesel U., Flohr K., Greulich B., Freytag G., Kolb-Bachofen V. Cell mediated immunity to islet cells: lessons from animal studies. Behring Inst Mitt. 1984 Jul;(75):33–38. [PubMed] [Google Scholar]
  10. Kuff E. L., Fewell J. W. Intracisternal A-particle gene expression in normal mouse thymus tissue: gene products and strain-related variability. Mol Cell Biol. 1985 Mar;5(3):474–483. doi: 10.1128/mcb.5.3.474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kuff E. L., Smith L. A., Lueders K. K. Intracisternal A-particle genes in Mus musculus: a conserved family of retrovirus-like elements. Mol Cell Biol. 1981 Mar;1(3):216–227. doi: 10.1128/mcb.1.3.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  13. Leiter E. H., Bedigian H. G. Intracisternal A-particles in genetically diabetic mice: identification in pancreas and induction in cultured beta cells. Diabetologia. 1979 Sep;17(3):175–185. doi: 10.1007/BF01219746. [DOI] [PubMed] [Google Scholar]
  14. Leiter E. H., Coleman D. L., Eppig J. J. Endocrine pancreatic cells of postnatal "diabetes" (db) mice in cell culture. In Vitro. 1979 Jul;15(7):507–521. doi: 10.1007/BF02618153. [DOI] [PubMed] [Google Scholar]
  15. Leiter E. H., Kuff E. L. Intracisternal Type A particles in murine pancreatic B cells. Immunocytochemical demonstration of increased antigen (p73) in genetically diabetic mice. Am J Pathol. 1984 Jan;114(1):46–55. [PMC free article] [PubMed] [Google Scholar]
  16. Leiter E. H. Type C retrovirus production by pancreatic beta cells. Association with accelerated pathogenesis in C3H-db/db ("Diabetes") mice. Am J Pathol. 1985 Apr;119(1):22–32. [PMC free article] [PubMed] [Google Scholar]
  17. Like A. A., Chick W. L. Studies in the diabetic mutant mouse. II. Electron microscopy of pancreatic islets. Diabetologia. 1970 Jun;6(3):216–242. doi: 10.1007/BF01212232. [DOI] [PubMed] [Google Scholar]
  18. Lueders K. K., Kuff E. L. Synthesis and turnover of intracisternal A-particle structural protein in cultured neuroblastoma cells. J Biol Chem. 1975 Jul 10;250(13):5192–5199. [PubMed] [Google Scholar]
  19. Meade C. J., Brandon D. R., Smith W., Simmonds R. G., Harris S., Sowter C. The relationship between hyperglycaemia and renal immune complex deposition in mice with inherited diabetes. Clin Exp Immunol. 1981 Jan;43(1):109–120. [PMC free article] [PubMed] [Google Scholar]
  20. Meissner H. P., Preissler M. Glucose-induced changes of the membrane potential of pancreatic B-cells: their significance for the regulation of insulin release. Adv Exp Med Biol. 1979;119:97–107. doi: 10.1007/978-1-4615-9110-8_15. [DOI] [PubMed] [Google Scholar]
  21. Schwizer R. W., Leiter E. H., Evans R. Macrophage-mediated cytotoxicity against cultured pancreatic islet cells. Transplantation. 1984 Jun;37(6):539–544. doi: 10.1097/00007890-198406000-00002. [DOI] [PubMed] [Google Scholar]
  22. Weringer E. J., Like A. A. Immune attack on pancreatic islet transplants in the spontaneously diabetic BioBreeding/Worcester (BB/W) rat is not MHC restricted. J Immunol. 1985 Apr;134(4):2383–2386. [PubMed] [Google Scholar]

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