On the dynamics of the human endocrine pancreas and potential consequences for the development of type 1 diabetes

Abstract

Little is known about the human islet life span, and beta-cell neogenesis is generally considered rare in adults. However, based on available data on beta-cell proliferation, calculations can be made suggesting that the dynamics of the endocrine pancreas is considerable even during adulthood, with islet neogenesis and a sustained increase in size of already formed islets. Islet-associated hemorrhages, frequently observed in most mammals including humans, could account for a considerable loss of islet parenchyma balancing the constant beta-cell proliferation. Notably, in subjects with type 1 diabetes, periductal accumulation of leukocytes and fibrosis is frequently observed, findings that are likely to negatively affect islet neogenesis from endocrine progenitor cells present in the periductal area. Impaired neogenesis would disrupt the balance, result in loss of islet mass, and eventually lead to beta-cell deficiency and compromised glucose metabolism, with increased islet workload and blood perfusion of remaining islets. These changes would impose initiation of a vicious circle further increasing the frequency of vascular events and hemorrhages within remaining islets until the patient eventually loses all beta-cells and becomes c-peptide negative.

Transcriptional analysis of islets of Langerhans from organ donors of different ages

“…These cells might represent a subpopulation of cells still capable of proliferation [ 38 ]. Even if only a fraction of a percent of the islet cells divide at a given time this would renew the entire endocrine pancreas in a matter of years [ 39 ].…”

Higher ultraviolet radiation during early life is associated with lower risk of childhood type 1 diabetes among boys

“…During this time, baseline beta cell mass is determined, and beta cell differentiation occurs 19 . At this time of beta cell development, low sun exposure could negatively impact islet neogenesis, resulting in reduced islet mass and ultimately beta cell deficiency and compromised glucose metabolism 20 . A recent systematic review suggests that exposure to UVR can modulate metabolic function in humans 21 .…”

Transcriptional profiles of human islet and exocrine endothelial cells in subjects with or without impaired glucose metabolism

“…It has previously been hypothesized that islets have a natural progression where they grow until the metabolic demand exceeds the vascular supply and a vascular catastrophe occurs 25 . The results presented herein are consistent with this hypothesis.…”