Insulin’s other life: an autoantigen in type 1 diabetes

Stuart I Mannering; Pushpak Bhattacharjee

doi:10.1111/imcb.12442

journal article Feb 22, 2021

Insulin’s other life: an autoantigen in type 1 diabetes

Stuart I Mannering

Pushpak Bhattacharjee

Immunology & Cell Biology Vol. 99 No. 5 pp. 448-460 · Wiley

View at Publisher Save 10.1111/imcb.12442

Abstract

AbstractOne hundred years ago, Frederick Banting, John Macleod, Charles Best and James Collip, and their collaborators, discovered insulin. This discovery paved the way to saving countless lives and ushered in the “Insulin Era.” Since the discovery of insulin, we have made enormous strides in understanding its role in metabolism and diabetes. Insulin has played a dramatic role in the treatment of people with diabetes; particularly type 1 diabetes (T1D). Insulin replacement is a life‐saving therapy for people with T1D and some with type 2 diabetes. T1D is an autoimmune disease caused by the T‐cell‐mediated destruction of the pancreatic insulin‐producing beta cells that leads to a primary insulin deficiency. It has become increasingly clear that insulin, and its precursors preproinsulin (PPI) and proinsulin (PI), can play another role—not as a hormone but as an autoantigen in T1D. Here we review the role played by the products of the INS gene as autoantigens in people with T1D. From many elegant animal studies, it is clear that T‐cell responses to insulin, PPI and PI are essential for T1D to develop. Here we review the evidence that autoimmune responses to insulin and PPI arise in people with T1D and discuss the recently described neoepitopes derived from the products of the insulin gene. Finally, we look forward to new approaches to deliver epitopes derived from PPI, PI and insulin that may allow immune tolerance to pancreatic beta cells to be restored in people with, or at risk of, T1D.

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Details

Published: Feb 22, 2021
Vol/Issue: 99(5)
Pages: 448-460
License: View

Authors

S

Stuart I Mannering

Immunology and Diabetes Unit St. Vincent’s Institute of Medical Research Fitzroy VIC Australia; Department of Medicine St. Vincent’s Hospital, University of Melbourne Fitzroy VIC Australia

P

Pushpak Bhattacharjee

Immunology and Diabetes Unit St. Vincent’s Institute of Medical Research Fitzroy VIC Australia

Funding

National Health and Medical Research Council Award: GNT123586

Cite This Article

Stuart I Mannering, Pushpak Bhattacharjee (2021). Insulin’s other life: an autoantigen in type 1 diabetes. Immunology & Cell Biology, 99(5), 448-460. https://doi.org/10.1111/imcb.12442

Insulin’s other life: an autoantigen in type 1 diabetes

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