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Altered processing of human insulin by B lymphocytes from an immunologically insulinresistant type I diabetic patient

Semple, John W. LU and Delovitch, Terry L. (1991) In Journal of Autoimmunity 4(2). p.277-289
Abstract

Immunologically insulin resistant (IIR) type I diabetic patients possess significantly elevated levels of anti-insulin serum autoantibodies. We investigated whether altered insulin processing by B lymphocytes contributes to this form of insulin resistance. A comparison was made of the 125I-labelled human insulin (HI) peptides processed by Epstein-Barr virus (EBV)-transformed B lymphocytes derived from HLA-identical and nonidentical IIR with non-IIR type I diabetic patients on insulin therapy and healthy non-diabetic individuals. Several peptides detected in the extracellular, membrane-associated and intracellular compartments of B cells from an IIR type I diabetic patient differed from those found in the corresponding... (More)

Immunologically insulin resistant (IIR) type I diabetic patients possess significantly elevated levels of anti-insulin serum autoantibodies. We investigated whether altered insulin processing by B lymphocytes contributes to this form of insulin resistance. A comparison was made of the 125I-labelled human insulin (HI) peptides processed by Epstein-Barr virus (EBV)-transformed B lymphocytes derived from HLA-identical and nonidentical IIR with non-IIR type I diabetic patients on insulin therapy and healthy non-diabetic individuals. Several peptides detected in the extracellular, membrane-associated and intracellular compartments of B cells from an IIR type I diabetic patient differed from those found in the corresponding compartments of B cells from two non-IIR type I diabetic patients and two normal individuals. These data suggest that HI is processed differently by B cells from an IIR type I diabetic patient compared with B cells from non-IIR type I diabetic patients and normal individuals. Further, we found that two of the five plasma-membrane associated processed HI peptides on the IIR patients' B cells were absent from the membrane compartments of the other B cell lines examined. Thus, it is possible that one or both of these peptides, unique to the IIR patients' B cells, consist of an immundominant epitope(s) that stimulates the production of insulin autoantibodies which mediate the onset of IIR in type I diabetes.

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type
Contribution to journal
publication status
published
subject
in
Journal of Autoimmunity
volume
4
issue
2
pages
277 - 289
publisher
Elsevier
external identifiers
  • pmid:1652968
  • scopus:0025897055
ISSN
0896-8411
DOI
10.1016/0896-8411(91)90024-7
language
English
LU publication?
no
id
229a267f-d2ee-4f94-bde2-125205cb701e
date added to LUP
2019-12-03 10:35:38
date last changed
2024-01-02 01:35:33
@article{229a267f-d2ee-4f94-bde2-125205cb701e,
  abstract     = {{<p>Immunologically insulin resistant (IIR) type I diabetic patients possess significantly elevated levels of anti-insulin serum autoantibodies. We investigated whether altered insulin processing by B lymphocytes contributes to this form of insulin resistance. A comparison was made of the <sup>125</sup>I-labelled human insulin (HI) peptides processed by Epstein-Barr virus (EBV)-transformed B lymphocytes derived from HLA-identical and nonidentical IIR with non-IIR type I diabetic patients on insulin therapy and healthy non-diabetic individuals. Several peptides detected in the extracellular, membrane-associated and intracellular compartments of B cells from an IIR type I diabetic patient differed from those found in the corresponding compartments of B cells from two non-IIR type I diabetic patients and two normal individuals. These data suggest that HI is processed differently by B cells from an IIR type I diabetic patient compared with B cells from non-IIR type I diabetic patients and normal individuals. Further, we found that two of the five plasma-membrane associated processed HI peptides on the IIR patients' B cells were absent from the membrane compartments of the other B cell lines examined. Thus, it is possible that one or both of these peptides, unique to the IIR patients' B cells, consist of an immundominant epitope(s) that stimulates the production of insulin autoantibodies which mediate the onset of IIR in type I diabetes.</p>}},
  author       = {{Semple, John W. and Delovitch, Terry L.}},
  issn         = {{0896-8411}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{2}},
  pages        = {{277--289}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Autoimmunity}},
  title        = {{Altered processing of human insulin by B lymphocytes from an immunologically insulinresistant type I diabetic patient}},
  url          = {{http://dx.doi.org/10.1016/0896-8411(91)90024-7}},
  doi          = {{10.1016/0896-8411(91)90024-7}},
  volume       = {{4}},
  year         = {{1991}},
}