Autoimmunity against INS-IGF2 expressed in human pancreatic islets.

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Autoimmunity against INS-IGF2 expressed in human pancreatic islets. / Kanatsuna, Norio; Taneera, Jalal; Vaziri Sani, Fariba; Wierup, Nils; Larsson, Helena; Delli, Ahmed; Skärstrand, Hanna; Balhuizen, Alexander; Bennet, Hedvig; Steiner, Donald F; Törn, Carina; Fex, Malin; Lernmark, Åke.

In: Journal of Biological Chemistry, Vol. 288, No. 40, 2013, p. 29013-29023.

Research output: Contribution to journalArticle

Harvard

Kanatsuna, N, Taneera, J, Vaziri Sani, F, Wierup, N, Larsson, H, Delli, A, Skärstrand, H, Balhuizen, A, Bennet, H, Steiner, DF, Törn, C, Fex, M & Lernmark, Å 2013, 'Autoimmunity against INS-IGF2 expressed in human pancreatic islets.', Journal of Biological Chemistry, vol. 288, no. 40, pp. 29013-29023. https://doi.org/10.1074/jbc.M113.478222

APA

Kanatsuna, N., Taneera, J., Vaziri Sani, F., Wierup, N., Larsson, H., Delli, A., Skärstrand, H., Balhuizen, A., Bennet, H., Steiner, D. F., Törn, C., Fex, M., & Lernmark, Å. (2013). Autoimmunity against INS-IGF2 expressed in human pancreatic islets. Journal of Biological Chemistry, 288(40), 29013-29023. https://doi.org/10.1074/jbc.M113.478222

CBE

Kanatsuna N, Taneera J, Vaziri Sani F, Wierup N, Larsson H, Delli A, Skärstrand H, Balhuizen A, Bennet H, Steiner DF, Törn C, Fex M, Lernmark Å. 2013. Autoimmunity against INS-IGF2 expressed in human pancreatic islets. Journal of Biological Chemistry. 288(40):29013-29023. https://doi.org/10.1074/jbc.M113.478222

MLA

Vancouver

Author

Kanatsuna, Norio ; Taneera, Jalal ; Vaziri Sani, Fariba ; Wierup, Nils ; Larsson, Helena ; Delli, Ahmed ; Skärstrand, Hanna ; Balhuizen, Alexander ; Bennet, Hedvig ; Steiner, Donald F ; Törn, Carina ; Fex, Malin ; Lernmark, Åke. / Autoimmunity against INS-IGF2 expressed in human pancreatic islets. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 40. pp. 29013-29023.

RIS

TY - JOUR

T1 - Autoimmunity against INS-IGF2 expressed in human pancreatic islets.

AU - Kanatsuna, Norio

AU - Taneera, Jalal

AU - Vaziri Sani, Fariba

AU - Wierup, Nils

AU - Larsson, Helena

AU - Delli, Ahmed

AU - Skärstrand, Hanna

AU - Balhuizen, Alexander

AU - Bennet, Hedvig

AU - Steiner, Donald F

AU - Törn, Carina

AU - Fex, Malin

AU - Lernmark, Åke

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

U2 - 10.1074/jbc.M113.478222

DO - 10.1074/jbc.M113.478222

M3 - Article

C2 - 23935095

VL - 288

SP - 29013

EP - 29023

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 1083-351X

IS - 40

ER -