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 beta-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 beta-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.

Keywords: PP-cell; islet architecture; islet of Langerhans; pancreatic β-cell; α-cell; δ-cell.

Figure 1

Multi-species comparison of islet structure and composition. Islets from various species are organized into a phylogenetic tree. Representative islets are pseudo-colored models of actual islets based on immunohistochemical images composed of α-cells (red), β-cells (green) and δ-cells (blue). The following species are shown: mouse (Mus musculus); human (Homo sapiens sapiens); rhesus macaque (Macaca mulatta); cat (Felis domesticus); dog (Canis lupus familiaris); fur seal (Arctocephalus pusillus); Egyptian fruit bat (Rousettus aegyptiacus); horse (Equus ferus caballus); cattle (Bos taurus); domestic goat (Capra aegagrus hircus); domestic sheep (Ovis aries); domestic pig (Sus domesticus); European rabbit (Oryctolagus cuniculus); striped hyena (Hyaena hyaena); water buffalo (Bubalus bubalis); beluga whale (Delphinapterus leucas); African elephant (Loxodonta africana); three-toed sloth (Bradypus variegatus); common brushtail opossum (Trichosurus vulpecula); zebra finch (Taeniopygia guttata); European asp (Vipera aspis); northern leopard frog (Rana pipiens) and rainbow trout (Salmo gairdneri). Note that high-quality images were not available for the echidna and camel. No information on δ-cells was available for the beluga whale. The phylogenetic tree was derived from work by Miller et al.

Figure 2

Comparison of mouse and human islets under various pathophysiological conditions. Mouse and human islets under various pathophysiological conditions are shown; α-cells (red), β-cells (green), and δ-cells (blue) based on immunohistochemical images. (A) Wild-type mouse (6 mo). (B) Pregnant mouse (3 mo). (C) ob/ob mouse (15 wk). (D) db/db mouse (15 wk). (E) Neonatal mouse (P14). (F) NOD mouse (40 wk). Note that lymphocytes (shown in gray) infiltrate the islet replacing the majority of the endocrine cells. (G) Normal human (41 yr). (H) Type-2 diabetic human. Note that islets from patients with type 2 diabetes often contain acellular amyloid deposits as shown in pink.