Autoimmunity against INS-IGF2 expressed in human pancreatic islets.

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.

• Författare: 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
• Avdelning/ar: Celiaki och diabetes; Institutionen för kliniska vetenskaper, Malmö; Neuroendokrin cellbiologi; Pediatrisk endokrinologi; EXODIAB: Excellence of Diabetes Research in Sweden
• Publiceringsår: 2013
• Språk: Engelska
• Sidor: 29013-29023
• Publikation/Tidskrift/Serie: Journal of Biological Chemistry
• Volym: 288
• Issue: 40
• Fulltext: - 1 MB; Download statistics
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/23935095?dopt=Abstract; http://dx.doi.org/10.1074/jbc.M113.478222
• Dokumenttyp: Artikel i tidskrift
• Förlag: American Society for Biochemistry and Molecular Biology
• Ämne: Endocrinology and Diabetes
• Status: Published
• Forskningsgrupp: Celiac Disease and Diabetes Unit; Neuroendocrine Cell Biology; Paediatric Endocrinology
• ISBN/ISSN/Övrigt: ISSN: 1083-351X