100 YEARS OF INSULIN: Pancreas pathology in type 1 diabetes: an evolving story

Abstract

We review the current knowledge of pancreas pathology in type 1 diabetes. During the last two decades dedicated efforts towards the recovery of pancreas from deceased patients with type 1 diabetes have promoted significant advances in the characterization of the pathological changes associated with this condition. The implementation autoantibody screening among organ donors has also allowed examining pancreas pathology in the absence of clinical disease, but in the presence of serological markers of autoimmunity. The assessment of key features of pancreas pathology across various disease stages allows driving parallels with clinical disease stages. The main pathological abnormalities observed in the pancreas with type 1 diabetes are beta cell loss, insulitis, and more recently hyperexpression of HLA class I and class II molecules have been reproduced and validated. Additionally, there are changes affecting extracellular matrix components, evidence of viral infections, inflammation, and ER stress, which could contribute to beta cell dysfunction and the stimulation of apoptosis and autoimmunity. The increasing appreciation that beta cell loss can be less severe at diagnosis than previously estimated, the coexistence of beta cell dysfunction, and the persistence of key features of pancreas pathology for years after diagnosis impact the perception of the dynamics of this chronic process. The emerging information is helping identifying novel therapeutic targets and have implications for the design of clinical trials.

Progress in islet transplantation is more important than ever

“…Particularly, with the coronavirus pandemic and in its aftermath, there might be a further increase in diabetes mellitus, including T1DM. We and others have shown that the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infects cells of both the endocrine and exocrine pancreas, which might lead to necroptotic cell death 5 , as previously observed for enteroviruses 4 . The Centers for Disease Control and Prevention ( CDC ) have reported an increased risk of new-onset diabetes mellitus in children and adolescents after having COVID-19.…”

“…Adding to the need for regenerative therapies, the incidence of T1DM is also rapidly increasing worldwide, reflecting the increasing role of environmental factors over genetic factors 4 . Particularly, with the coronavirus pandemic and in its aftermath, there might be a further increase in diabetes mellitus, including T1DM.…”

Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond

“…T1D is an autoreactive disease arising from immune destruction of insulin-producing pancreatic β cells ( 359 ). Both NEU1 and NEU3 have been implicated in the pathogenesis of T1D.…”

Functional Impact of Risk Gene Variants on the Autoimmune Responses in Type 1 Diabetes

“…T1D patients donating tissues for research helped to collect a significant evidence that T1D pathogenesis can follow different individual scenarios but also that mechanisms described in animal models are not all or not just as strongly present in the human immune system. For example, the infiltration of immune cells around the islet of Langerhans, designated as insulitis, in which activated CD4+ T cells control macrophages to induce killing of the β-cells by cytokines and reactive oxygen species, is clearly evident in mice ( 23 ) but not evident in human pancreas ( 24 , 25 ). Cytotoxic CD8+ T cells are essential for the ultimate destruction of β-cells, while their antigen specificity varies between patients ( 4 , 26 ).…”