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Title

Partial diversion of a mutant proinsulin (B10 aspartic acid) from the regulated to the constitutive secretory pathway in transfected AtT-20 cells

Authors
Gross, D. J.
Kahn, C. R.
Weir, G. C.
Villa-Komaroff, L.
Published in Proceedings of the National Academy of Sciences. 1989, vol. 86, no. 11, p. 4107-4111
Abstract A patient with type II diabetes associated with hyperproinsulinemia has been shown to have a point mutation in one insulin gene allele, resulting in replacement of histidine with aspartic acid at position 10 of the B-chain. To investigate the basis of the proinsulin processing defect, we introduced an identical mutation in the rat insulin II gene and expressed both the normal and the mutant genes in the AtT-20 pituitary corticotroph cell line. Cells expressing the mutant gene showed increased secretion of proinsulin relative to insulin and rapid release of newly synthesized proinsulin. Moreover, the mutant cell lines did not store the prohormone nor did they release it upon stimulation with secretagogues. These data indicate that a significant fraction of the mutant prohormone is released via the constitutive secretory pathway rather than the regulated pathway, thereby bypassing granule-related processing and regulated release.
Keywords AnimalsAspartic AcidCell LineGenesGenetic VectorsInsulin/secretionMutationPituitary NeoplasmsPlasmidsProinsulin/biosynthesis/ genetics/secretionRatsTransfection
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PMID: 2657740
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GROSS, D. J. et al. Partial diversion of a mutant proinsulin (B10 aspartic acid) from the regulated to the constitutive secretory pathway in transfected AtT-20 cells. In: Proceedings of the National Academy of Sciences, 1989, vol. 86, n° 11, p. 4107-4111. https://archive-ouverte.unige.ch/unige:8767

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Deposited on : 2010-07-12

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