No mantle formation in rodent islets—The prototype of islet revisited

Abstract

Emerging reports on human islets emphasize distinct differences from the widely accepted prototype of rodent islets, raising questions over their suitability for human studies. Here we aim at elucidating architectural differences and similarities of human versus rodent islets. The cellular composition and architecture of human and rodent islets were compared through three-dimensional (3D) reconstructions. Physiological and pathological changes were examined using islets from various mouse models such as non-obese diabetic (NOD), ob/ob, db/db mice and during pregnancy. A subpopulation of human islets is composed of clusters of alpha-cells within the central beta-cell cores, while the overall proportion of alpha-cells varies among islets. In mouse islets under normal conditions, alpha-cells are localized in the islet periphery, but they do not envelop the entire betacell core, so that beta-cells are exposed on the outer layer of the islet, as in most human islets. Also, an increased proportion of alpha-cells within the central core is observed in the pancreas of mouse models exhibiting increased demand for insulin. In summary, human and mouse islets share common architectural features as endocrine micro-organs. Since these may hold a key to better understanding islet plasticity, our concept of the prototypic islet should be revised.

The Human GLP-1 Analogs Liraglutide and Semaglutide: Absence of Histopathological Effects on the Pancreas in Nonhuman Primates

“…The fraction of the four endocrine cell types in our study is in agreement with data from human pancreata and a descriptive study in Cynomolgus monkeys (31)(32)(33)(34). The intraislet organization of the band non-b-cells was random, with no clear rodent-like mantle and core, but with a more complex subunit structure of mantles and cores, as characteristic for nonhuman primates and humans (23,35,36). In all groups, including the controls, the distribution of a-cells was identical in islets and islets-like structures of variable size.…”

“…Additionally, the morphology of nonhuman primate islets is like that seen in humans and different from rodents (23). Quantitative histology was used to assess changes in the mass of different pancreatic tissue components, taking the three-dimensional structure of the organ into consideration (24).…”

Beta-cell hubs maintain Ca2+ oscillations in human and mouse islet simulations

“…Interestingly, the characteristics of islets from mouse models of diabetes are more similar to human islets. 70 Therefore, the reduced insulin output from these strains may in part result from hubs experiencing a greater demand in an architecture more sensitive to hub disruption.…”

Adaptaciones de las poblaciones celulares alfa y beta del islote de Langerhans a la preñez en ratonas C57BL/6

“…Motivados además porque, hasta el momento, se conoce muy poco de las adaptaciones de la célula alfa durante la preñez. Hasta la fecha se ha observado, en estudios anteriores, que veremos más en detalle en el próximo apartado, un aumento en el área de la masa de célula alfa (Kharouta et al, 2009), así como un aumento del tamaño celular (Xu et al, 2015).…”

“…Tras una profunda revisión de la literatura existente, los dos estudios que hablan sobre esta cuestión de forma poco detallada son los que presento a continuación. Se ha descrito un aumento de un 6% en el área de célula alfa en ratones (calculado como ratio entre célula alfa/célula beta), respecto de un control wild-type, encontrando el máximo aumento alrededor del día 15 de gestación, para decrecer hasta niveles normales justo antes del parto (Kharouta et al, 2009). Sin embargo, se aporta poca información en dicho estudio sobre cómo se obtuvieron estos resultados.…”