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J Biol Chem. 2013 Oct 4;288(40):29013-23. doi: 10.1074/jbc.M113.478222. Epub 2013 Aug 9.

Autoimmunity against INS-IGF2 protein expressed in human pancreatic islets.

Author information

  • 1From the Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Skåne University Hospital SUS, SE-205 02 Malmö, Sweden and.

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 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.

KEYWORDS:

Antibodies; Antigen; Beta Cell; Diabetes; Insulin; Insulin-like Growth Factor (IGF); Pancreatic Islets; Radioimmune Assays

PMID:
23935095
[PubMed - indexed for MEDLINE]
PMCID:
PMC3789998
[Available on 2014/10/4]
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