Islet architecture: A comparative study

Abstract

Emerging reports on the organization of the different hormone-secreting cell types (alpha, glucagon; beta, insulin; and delta, somatostatin) in human islets have emphasized the distinct differences between human and mouse islets, raising questions about the relevance of studies of mouse islets to human islet physiology. Here, we examine the differences and similarities between the architecture of human and mouse islets. We studied islets from various mouse models including ob/ob and db/db and pregnant mice. We also examined the islets of monkeys, pigs, rabbits and birds for further comparisons. Despite differences in overall body and pancreas size as well as total beta-cell mass among these species, the distribution of their islet sizes closely overlaps, except in the bird pancreas in which the delta-cell population predominates (both in singlets and clusters) along with a small number of islets. Markedly large islets (>10,000 mum(2)) were observed in human and monkey islets as well as in islets from ob/ob and pregnant mice. The fraction of alpha-, beta- and delta-cells within an islet varied between islets in all the species examined. Furthermore, there was variability in the distribution of alpha- and delta-cells within the same species. In summary, human and mouse islets share common architectural features that may reflect demand for insulin. Comparative studies of islet architecture may lead to a better understanding of islet development and function.

Keywords: diabetes; insulin resistance; pancreatic islets; pregnancy; α-cells; β-cells; δ-cells.

Figure 1

Immunohistochemical analysis of pancreatic islets from various species. (A) Islet size distribution across several species including ob/ob, db/db and pregnant mice. Note the similar distribution pattern within the closely overlapping range in size among species. (B) Immunofluorescent staining of insulin (green), glucagon (red), somatostatin (orange) and nuclei (blue) showing an overview of islet distribution in each species. (a) Human, (b) Rhesus monkey, (c) Pig, (d) Rabbit, (e) Mouse, (f) Song bird. Scale in μm.

Figure 2

Plasticity and variability of islet in various species. Representative islets of each species are shown on the left, and distribution of islets according to endocrine cell composition is plotted in 3D on the right. Each dot depicts a single islet. Note the diversity of islet size, shape and cell composition among species as well as within the same species, demonstrating the plasticity and variability of islets. For birds, islets with beta-cells were selectively shown. Scale in μm.

Figure 3

Mathematical analysis on islet size distribution and cellular composition among species. Top: lognormal probability density functions are fitted to histograms of islet effective diameters (i.e., a parameter that depicts the same area of a theoretical perfect circle) for each species. Bottom: cellular composition ratios (β-cells in green, α-cells in red and δ-cells in blue) for each islet effective diameter bin.

Figure 4

Changes in islet architecture and composition under pathophysiological conditions such as obesity, pregnancy and diabetes. (A) Overviews of islet distribution in ob/ob (a), pregnant (b) and db/db (c) mice. Scale in μm. (B) Corresponding 3D scatter plots to images in (A) are shown. Distribution of endocrine cell composition is compared between human and mice under normal and pathophysiological conditions (lower left). Note the similarities in islet size distribution and islet composition between humans and mice.