The pathogenic "symphony" in type 1 diabetes: A disorder of the immune system, β cells, and exocrine pancreas

Cell Metab. 2023 Sep 5;35(9):1500-1518. doi: 10.1016/j.cmet.2023.06.018. Epub 2023 Jul 20.


Type 1 diabetes (T1D) is widely considered to result from the autoimmune destruction of insulin-producing β cells. This concept has been a central tenet for decades of attempts seeking to decipher the disorder's pathogenesis and prevent/reverse the disease. Recently, this and many other disease-related notions have come under increasing question, particularly given knowledge gained from analyses of human T1D pancreas. Perhaps most crucial are findings suggesting that a collective of cellular constituents-immune, endocrine, and exocrine in origin-mechanistically coalesce to facilitate T1D. This review considers these emerging concepts, from basic science to clinical research, and identifies several key remaining knowledge voids.

Keywords: autoimmunity; endocrinology; exocrine pancreas; immune cells; inflammation; insulin; insulitis; islet of Langerhans; type 1 diabetes.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 1*
  • Humans
  • Immune System
  • Insulin-Secreting Cells* / pathology
  • Islets of Langerhans* / pathology
  • Pancreas / pathology
  • Pancreas, Exocrine* / pathology