Autoimmunity against INS-IGF2 Protein Expressed in Human Pancreatic Islets

Norio Kanatsuna, Jalal Taneera, Fariba Vaziri-Sani, Nils Wierup, Helena Elding Larsson, Ahmed Delli, Hanna Skarstrand, Alexander Balhuizen, Hedvig Bennet, Donald F. Steiner, Carina Torn, Malin Fex, Ake Lernmark

Forskningsoutput: TidskriftsbidragArtikelPeer review

21 Citeringar (Scopus)

Sammanfattning

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 the expression of INS-IGF2 in human pancreatic islets and autoantibodies in newly diagnosed children with type 1 diabetes and controls. INS-IGF2, expressed primarily in beta cells, showed higher levels of expression in islets from normal compared with 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 patients with type 1 diabetes (n = 304) compared with 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.

OriginalspråkEngelska
Sidor (från-till)29013-29023
Antal sidor10
TidskriftJournal of Biological Chemistry
Volym288
Utgåva40
DOI
StatusPublicerad - 2013
Externt publiceradJa

Nationell ämneskategori

  • Cell- och molekylärbiologi (30108)
  • Immunologi inom det medicinska området (30110)

Fingeravtryck

Fördjupa i forskningsämnen för ”Autoimmunity against INS-IGF2 Protein Expressed in Human Pancreatic Islets”. Tillsammans bildar de ett unikt fingeravtryck.

Citera det här