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.
journal_name
Proc Natl Acad Sci U S Aauthors
Gross DJ,Halban PA,Kahn CR,Weir GC,Villa-Komaroff Ldoi
10.1073/pnas.86.11.4107subject
Has Abstractpub_date
1989-06-01 00:00:00pages
4107-11issue
11eissn
0027-8424issn
1091-6490journal_volume
86pub_type
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