Insulin-secreting non-islet cells are resistant to autoimmune destruction.
- 6 August 1996
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 93 (16) , 8595-8600
- https://doi.org/10.1073/pnas.93.16.8595
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 beta cells. However, in contrast to the insulin-producing islet beta 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 beta-cell replacement therapy for the treatment of insulin-dependent diabetes mellitus.Keywords
This publication has 25 references indexed in Scilit:
- Unraveling Immune PrivilegeScience, 1995
- Insulin‐specific T cells are a predominant component of islet infiltrates in pre‐diabetic NOD miceEuropean Journal of Immunology, 1994
- Differential Expression of Glutamic Acid Decarboxylase in Rat and Human IsletsDiabetes, 1993
- Identification of a cDNA encoding a second putative prohormone convertase related to PC2 in AtT20 cells and islets of Langerhans.Proceedings of the National Academy of Sciences, 1991
- DMA mutagenesis and recombinationNature, 1990
- Partial diversion of a mutant proinsulin (B10 aspartic acid) from the regulated to the constitutive secretory pathway in transfected AtT-20 cells.Proceedings of the National Academy of Sciences, 1989
- Pituitary-specific expression and glucocorticoid regulation of a proopiomelanocortin fusion gene in transgenic mice.Proceedings of the National Academy of Sciences, 1988
- Characterization of the two nonallelic genes encoding mouse preproinsulinJournal of Molecular Evolution, 1986
- Expressing a human proinsulin cDNA in a mouse ACTH-secreting cell. Intracellular storage, proteolytic processing, and secretion on stimulationCell, 1983
- Islet-Cell Antibodies and Beta-Cell Function in Monozygotic Triplets and Twins Initially Discordant for Type I Diabetes MellitusNew England Journal of Medicine, 1983