Human Islet Morphology Revisited: Human and Rodent Islets Are Not So Different After All

Abstract

There has been great interest in understanding how human islets differ from rodent islets. Three major issues about human islet morphology have remained controversial over recent decades: 1) the proportion of the islet made up of β-cells; 2) whether islet cell types have a non-random mantle-core pattern, as seen in rodents, or are randomly scattered throughout the islet; 3) the relation of the different cell types to the blood vessels within the islet, which has implications for intraislet function. We re-examined these issues on immunostained sections of non-diabetic adult human pancreas. The composition of the islets can vary by the analysis method (number vs volume) and by the sampling of islets by size. The majority of adult human islets have clear, non-random clustering of β-cells and blood vessels that penetrate into the β-cell cores. We conclude that although there is far more variability in islet composition both within each human pancreas and among different human pancreas than in rodent pancreas, the islet architecture is not so different between the species. The intrapancreatic variability raises important questions about how islets evolve and function throughout life and how this might relate to the pathogenesis of diabetes.

Keywords: human islets; islet architecture; islet composition; mantle-core.

Figure 1.

Representative islets in pancreas from donor H0015 immunostained for glucagon (brown) showed great variability in islet composition, both in the proportion of cell types and the clarity of β-cell core arrangement. The smaller islets resemble those of rodents with a clear mantle-core pattern. However, as shown here, even the larger islets with fewer β-cells have a discernible clustering of β-cells. Scale, 50 µm.

Figure 2.

Representative islets in pancreas from donor H0021 immunostained for glucagon (brown) showed greater variability in islet composition, both in the proportion of cell types and the clarity of β-cell core arrangement. Some of the large islets have mainly glucagon staining cells, with few β-cells (here unstained). Scale, 50 µm.

Figure 3.

Representative islets in pancreas from donor H0019 immunostained for glucagon (brown) showed a clear pattern of small subunits resembling that of the rodent mantle-core islet organization in most of the islets of all sizes. Scale, 50 µm.

Figure 4.

Islets in pancreas from donor H0021 immunofluorescently stained for insulin (red) and non-β-cells (glucagon and somatostatin; green) show clear clustering of β-cells with surrounding non-β-cells. Additionally, apparent vascular channels (white asterisks) are seen penetrating in the β-cell clusters. Scale, 20 µm.

Figure 5.

Even small islets of pancreas from donor H0021 show blood vessels, here visualized by immunostaining for smooth muscle actin and CD34 (blue), coursing into clumps of β-cells (red) with no glucagon cells (green) nearby. Scale, 20 µm.