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Autoimmunity against INS-IGF2 expressed in human pancreatic islets.

Kanatsuna, Norio LU ; Taneera, Jalal LU ; Vaziri Sani, Fariba LU ; Wierup, Nils LU ; Larsson, Helena LU ; Delli, Ahmed LU ; Skärstrand, Hanna LU ; Balhuizen, Alexander LU ; Bennet, Hedvig LU and Steiner, Donald F, et al. (2013) In Journal of Biological Chemistry 288(40). p.29013-29023
Abstract
Insulin is a major autoantigen in islet autoimmunity and progression to type 1 diabetes. It has been suggested that the insulin B-chain may be critical to insulin autoimmunity in type 1 diabetes. INS-IGF2 consists of the preproinsulin signal peptide, the insulin B-chain and eight amino acids of the C-peptide in addition to 138 amino acids from the IGF2 gene. We aimed to determine 1) expression of INS-IGF2 in human pancreatic islets and 2) autoantibodies in newly diagnosed type 1 diabetes children and controls. INS-IGF2, expressed primarily in beta cells, showed higher levels of expression in islets from normal compared to donors with either type 2 diabetes (p=0.006) or high HbA1c levels (p<0.001). INS-IGF2 autoantibody levels were... (More)
Insulin is a major autoantigen in islet autoimmunity and progression to type 1 diabetes. It has been suggested that the insulin B-chain may be critical to insulin autoimmunity in type 1 diabetes. INS-IGF2 consists of the preproinsulin signal peptide, the insulin B-chain and eight amino acids of the C-peptide in addition to 138 amino acids from the IGF2 gene. We aimed to determine 1) expression of INS-IGF2 in human pancreatic islets and 2) autoantibodies in newly diagnosed type 1 diabetes children and controls. INS-IGF2, expressed primarily in beta cells, showed higher levels of expression in islets from normal compared to donors with either type 2 diabetes (p=0.006) or high HbA1c levels (p<0.001). INS-IGF2 autoantibody levels were increased in newly diagnosed type 1 diabetes patients (n=304) compared to healthy controls (n=355; p<0.001). Displacement with cold insulin and INS-IGF2 revealed that more patients than controls had doubly reactive insulin-INS-IGF2 autoantibodies. These data suggest that INS-IGF2, which contains the preproinsulin signal peptide, the B-chain and eight amino acids of the C-peptide may be an autoantigen in type 1 diabetes. INS-IGF2 and insulin may share autoantibody binding sites, thus complicating the notion that insulin is the primary autoantigen in type 1 diabetes. (Less)
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Contribution to journal
publication status
published
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in
Journal of Biological Chemistry
volume
288
issue
40
pages
29013 - 29023
publisher
ASBMB
external identifiers
  • wos:000330298800055
  • pmid:23935095
  • scopus:84885130819
ISSN
1083-351X
DOI
10.1074/jbc.M113.478222
language
English
LU publication?
yes
id
ca46811b-e1de-40ea-9346-7c5666e80e91 (old id 4005927)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23935095?dopt=Abstract
date added to LUP
2013-09-03 15:23:01
date last changed
2019-03-19 01:00:52
@article{ca46811b-e1de-40ea-9346-7c5666e80e91,
  abstract     = {Insulin is a major autoantigen in islet autoimmunity and progression to type 1 diabetes. It has been suggested that the insulin B-chain may be critical to insulin autoimmunity in type 1 diabetes. INS-IGF2 consists of the preproinsulin signal peptide, the insulin B-chain and eight amino acids of the C-peptide in addition to 138 amino acids from the IGF2 gene. We aimed to determine 1) expression of INS-IGF2 in human pancreatic islets and 2) autoantibodies in newly diagnosed type 1 diabetes children and controls. INS-IGF2, expressed primarily in beta cells, showed higher levels of expression in islets from normal compared to donors with either type 2 diabetes (p=0.006) or high HbA1c levels (p&lt;0.001). INS-IGF2 autoantibody levels were increased in newly diagnosed type 1 diabetes patients (n=304) compared to healthy controls (n=355; p&lt;0.001). Displacement with cold insulin and INS-IGF2 revealed that more patients than controls had doubly reactive insulin-INS-IGF2 autoantibodies. These data suggest that INS-IGF2, which contains the preproinsulin signal peptide, the B-chain and eight amino acids of the C-peptide may be an autoantigen in type 1 diabetes. INS-IGF2 and insulin may share autoantibody binding sites, thus complicating the notion that insulin is the primary autoantigen in type 1 diabetes.},
  author       = {Kanatsuna, Norio and Taneera, Jalal and Vaziri Sani, Fariba and Wierup, Nils and Larsson, Helena and Delli, Ahmed and Skärstrand, Hanna and Balhuizen, Alexander and Bennet, Hedvig and Steiner, Donald F and Törn, Carina and Fex, Malin and Lernmark, Åke},
  issn         = {1083-351X},
  language     = {eng},
  number       = {40},
  pages        = {29013--29023},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Autoimmunity against INS-IGF2 expressed in human pancreatic islets.},
  url          = {http://dx.doi.org/10.1074/jbc.M113.478222},
  volume       = {288},
  year         = {2013},
}