Insulin-secreting non-islet cells are resistant to autoimmune destruction

Myra A. Lipes, Eric M. Cooper, Robert Skelly, Christopher J. Rhodes, Edward Boschetti, Gordon C. Weir, Alberto M. Davalli

Research output: Contribution to journalArticle

Abstract

Transgenic nonobese diabetic mice were created in which insulin expression was targeted to proopiomelanocortin-expressing pituitary cells. Proopiomelanocortin-expressing intermediate lobe pituitary cells efficiently secrete fully processed, mature insulin via a regulated secretory pathway, similar to islet β cells. However, in contrast to the insulin-producing islet β cells, the insulin-producing intermediate lobe pituitaries are not targeted or destroyed by cells of the immune system. Transplantation of the transgenic intermediate lobe tissues into diabetic nonobese diabetic mice resulted in the restoration of near-normoglycemia and the reversal of diabetic symptoms. The absence of autoimmunity in intermediate lobe pituitary cells engineered to secrete bona fide insulin raises the potential of these cell types for β-cell replacement therapy for the treatment of insulin- dependent diabetes mellitus.

Original languageEnglish
Pages (from-to)8595-8600
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number16
DOIs
Publication statusPublished - Aug 6 1996

Keywords

  • diabetes
  • insulin gene expression
  • intermediate pituitary
  • transgenic models

ASJC Scopus subject areas

  • General
  • Genetics

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  • Cite this

    Lipes, M. A., Cooper, E. M., Skelly, R., Rhodes, C. J., Boschetti, E., Weir, G. C., & Davalli, A. M. (1996). Insulin-secreting non-islet cells are resistant to autoimmune destruction. Proceedings of the National Academy of Sciences of the United States of America, 93(16), 8595-8600. https://doi.org/10.1073/pnas.93.16.8595