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Nils Wierup

Nils Wierup

Senior lecturer

Nils Wierup

Autoimmunity against INS-IGF2 expressed in human pancreatic islets.

Author

  • Norio Kanatsuna
  • Jalal Taneera
  • Fariba Vaziri Sani
  • Nils Wierup
  • Helena Larsson
  • Ahmed Delli
  • Hanna Skärstrand
  • Alexander Balhuizen
  • Hedvig Bennet
  • Donald F Steiner
  • Carina Törn
  • Malin Fex
  • Åke Lernmark

Summary, in English

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.

Department/s

  • Celiac Disease and Diabetes Unit
  • Department of Clinical Sciences, Malmö
  • Neuroendocrine Cell Biology
  • Paediatric Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2013

Language

English

Pages

29013-29023

Publication/Series

Journal of Biological Chemistry

Volume

288

Issue

40

Document type

Journal article

Publisher

American Society for Biochemistry and Molecular Biology

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes and Celiac Unit
  • Neuroendocrine Cell Biology
  • Paediatric Endocrinology

ISBN/ISSN/Other

  • ISSN: 1083-351X