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

Research output: Contribution to journalArticle

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 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.

Details

Authors
External organisations
  • University of Toronto
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)277-289
JournalJournal of Autoimmunity
Volume4
Issue number2
Publication statusPublished - 1991 Jan 1
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes