Pancreatic islet plasticity: Interspecies comparison of islet architecture and composition

Abstract

The pancreatic islet displays diverse patterns of endocrine cell arrangement. The prototypic islet, with insulin-secreting β-cells forming the core surrounded by other endocrine cells in the periphery, is largely based on studies of normal rodent islets. Recent reports on large animals, including humans, show a difference in islet architecture, in which the endocrine cells are randomly distributed throughout the islet. This particular species difference has raised concerns regarding the interpretation of data based on rodent studies to humans. On the other hand, further variations have been reported in marsupials and some nonhuman primates, which possess an inverted ratio of β-cells to other endocrine cells. This review discusses the striking plasticity of islet architecture and cellular composition among various species including changes in response to metabolic states within a single species. We propose that this plasticity reflects evolutionary acquired adaptation induced by altered physiological conditions, rather than inherent disparities between species.

Fetal endocannabinoids orchestrate the organization of pancreatic islet microarchitecture

“…Laboratory rodents present core-mantle islet morphology with an α cell mantle enwrapping its β cell-dense core (18). In contrast, the organization of α and β cells in adult human pancreatic islets is remarkably different (Fig.…”

“…This observation is significant because pancreatic islet morphology is evolutionarily varied (18), reflective of the lifestyle, energy expenditure, and body mass of vertebrate species. As such, mixed pancreatic islets are characteristic of humans and nonhuman primates (18,19) and suggest an evolutionary selection toward an anatomical microstructure that supports the increased dynamics of hormonal responses, especially in the presence of nutrient abundance. In rodents, reorganization of the core-mantle morphology of pancreatic islets, often interpreted as inadequate, might in fact (F1) Moreover, the correlated insulin/glucagon ratio was significantly increased upon high glucose.…”

“…Moreover, α and β cells in mature pancreatic islets express the molecular machinery for eCB metabolism together with CB 1 Rs and transient receptor potential cation channels, particularly subfamily V member 1 (TRPV1) (2,16,17). Understanding these developmental processes is also relevant to postnatal life because pancreatic α-and β-cell placement can be reconfigured upon metabolic demands in both rodents (18) and humans (19), altering the efficacy of endocrine responsiveness.…”

Fibrin supports human fetal islet-epithelial cell differentiation via p70s6k and promotes vascular formation during transplantation

“…Numerous articles have outlined signaling pathway differences between the rodent and human pancreas. [42][43][44] Also, the mTOR pathway has different effects on the islet cell cycle depending on the animal species. 45,46 In particular, stimulation of rodent islets with palmitate led to increased DNA synthesis (in an mTORdependent manner) in rodent islets, but not those isolated from humans.…”

On the coherent behavior of pancreatic beta cell clusters

“…Specifically beta cells are able to lower glycemic level by releasing insulin [1]. In rodents, these cells are clustered in the central core of the islet surrounded by peripheral alpha cells, and are coupled through specific connections, the gap junctions [2,3,4,5]. In response to glucose uptake from extracellular space, beta cells within the islet modify their membrane potential, exhibiting slow oscillations with superimposed action potentials (bursting activity) [1].…”