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

The Journal of biological chemistry 2013 Oct 04

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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.

Citation

Norio Kanatsuna, Jalal Taneera, Fariba Vaziri-Sani, Nils Wierup, Helena Elding Larsson, Ahmed Delli, Hanna Skärstrand, Alexander Balhuizen, Hedvig Bennet, Donald F Steiner, Carina Törn, Malin Fex, Åke Lernmark. Autoimmunity against INS-IGF2 protein expressed in human pancreatic islets. The Journal of biological chemistry. 2013 Oct 04;288(40):29013-23