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

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. Atkinson and Mirmira consider recent knowledge gains from studies of human pancreas that suggest immune, endocrine, and exocrine cells mechanistically coalesce to facilitate type 1 diabetes pathogenesis, portraying a more complex orchestration of this disease than was previously appreciated. [ABSTRACT FROM AUTHOR]