Autoimmunity against INS-IGF2 expressed in human pancreatic islets.
(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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https://lup.lub.lu.se/record/4005927
- author
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 288
- issue
- 40
- pages
- 29013 - 29023
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000330298800055
- pmid:23935095
- scopus:84885130819
- pmid:23935095
- 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
- 2016-04-01 09:50:03
- date last changed
- 2022-05-05 08:02:17
@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<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.}}, 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 = {{American Society for Biochemistry and Molecular Biology}}, series = {{Journal of Biological Chemistry}}, title = {{Autoimmunity against INS-IGF2 expressed in human pancreatic islets.}}, url = {{https://lup.lub.lu.se/search/files/1299463/4316508.pdf}}, doi = {{10.1074/jbc.M113.478222}}, volume = {{288}}, year = {{2013}}, }