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

Abstract

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.