From immunohistological to anatomical alterations of human pancreas in type 1 diabetes: New concepts on the stage

Abstract

The histological analysis of human pancreatic samples in type 1 diabetes (T1D) has been proven essential to move forward in the evaluation of in situ events characterizing T1D. Increasing availability of pancreatic tissues collected from diabetic multiorgan donors by centralized biorepositories, which have shared tissues among researchers in the field, has allowed a deeper understanding of T1D pathophysiology, using novel immunohistological and high-throughput methods. In this review, we provide a comprehensive update of the main recent advancements in the characterization of cellular and molecular events involving endocrine and exocrine pancreas as well as the immune system in the onset and progression of T1D. Additionally, we underline novel elements, which provide evidence that T1D pathological changes affect not only islet β-cells but also the entire pancreas.

SARS-CoV-2 receptor Angiotensin I-Converting Enzyme type 2 (ACE2) is expressed in human pancreatic β-cells and in the human pancreas microvasculature

“…Collagenase-isolated human pancreatic islets obtained from four different non-diabetic donors pancreata ( Table S1 ) showed ACE2 mRNA expression, as demonstrated by RT-Real-Time PCR raw cycle threshold (Ct) values, reporting a Ct range between 28-29 ( Figure 6B and 6F ). Since human pancreatic islets enzymatic isolation procedures may induce some changes in gene expression (45), we microdissected human islets from frozen pancreatic tissues obtained from five non-diabetic multiorgan donors recruited within INNODIA EUnPOD network (46) and evaluated ACE2 mRNA levels. The LCM procedure ( Figure S9B ) allowed us to extract high quality total RNA ( Figure S9C ) from human pancreatic islets directly obtained from their native microenvironment, thus maintaining transcriptional architecture.…”

Pancreatic Alpha-Cells Contribute Together With Beta-Cells to CXCL10 Expression in Type 1 Diabetes

“…Following acquisition of informed research consent, pancreata ( n = 3) were obtained from brain-dead multiorgan donors within the European Network for Pancreatic Organ Donors with Diabetes (EUnPOD) ( 2 ), a project launched in the context of the INNODIA consortium ( www.innodia.eu ). Whole pancreata were processed following standardized procedures at University of Pisa.…”

“…Type 1 diabetes (T1D) is an autoimmune disease, characterized by a progressive destruction of pancreatic insulin-producing beta-cells driven by autoreactive T-lymphocytes (1) and leading to chronic hyperglycemia and to the development of chronic complications (2).…”

SARS-CoV-2 Receptor Angiotensin I-Converting Enzyme Type 2 (ACE2) Is Expressed in Human Pancreatic β-Cells and in the Human Pancreas Microvasculature

“…Collagenase-isolated human pancreatic islets obtained from four different non-diabetic donors' pancreata (Table S1) showed ACE2 mRNA expression, as demonstrated by RT-Real-Time PCR raw cycle threshold (Ct) values, reporting a Ct range between 28 and 29 ( Figures 6B, F). Since human pancreatic islet enzymatic isolation procedures may induce some changes in gene expression (45), we microdissected human islets from frozen pancreatic tissues obtained from five non-diabetic multiorgan donors recruited within INNODIA EUnPOD network (46) and evaluated ACE2 mRNA levels. The LCM procedure ( Figure S9B) allowed us to extract high quality total RNA ( Figure S9C) from human pancreatic islets directly obtained from their native microenvironment, thus maintaining transcriptional architecture.…”