A 3D map of the islet routes throughout the healthy human pancreas

Abstract

Islets of Langerhans are fundamental in understanding diabetes. A healthy human pancreas from a donor has been used to asses various islet parameters and their three-dimensional distribution. Here we show that islets are spread gradually from the head up to the tail section of the pancreas in the form of contracted or dilated islet routes. We also report a particular anatomical structure, namely the cluster of islets. Our observations revealed a total of 11 islet clusters which comprise of small islets that surround large blood vessels. Additional observations in the peripancreatic adipose tissue have shown lymphoid-like nodes and blood vessels captured in a local inflammatory process. Our observations are based on regional slice maps of the pancreas, comprising of 5,423 islets. We also devised an index of sphericity which briefly indicates various islet shapes that are dominant throughout the pancreas.

Figure 1. Distribution of pancreatic islets.

(A) a two-dimensional distribution of pancreatic islets on each section (B1–B4) of the pancreas. The pancreas from the donor and the organizational scheme of the slices are also presented. Dorsal pancreas is represented by Bx[P1-P4] slides whereas the ventral pancreas is represented by Bx[P13–P16] slides. (B) the proportion of islets along the four sections. The pancreatic islet distribution on each histological slide depending on the islet number and their average area (μm²), it is shown for the: (C) head area (B1), (D) isthmus area (B2), (E) body area (B3), (F) tail area (B4). The mean surface area (μm²) of the islets is represented on the X-axis whereas the number of islets is represented on the Y-axis. The islet number and their average area per slice (B1–B4) it is shown for the: (J) head area (B1), (I) isthmus area (B2), (G) body area (B3), (H) tail area (B4). The trend lines in panels C to H use a polynomial of order 3. (K) distribution of islets ordered by size. For each slice (B1–4), the number of islets is represented on the X-axis whereas the surface area (μm²) of the islets is represented on the Y-axis. The diamond shaped points represent islets in the head area. The square shaped points represent islets in the neck area and the points with triangular shape represent islets in the body area. The circular shaped points represent islets in the tail area. (L) a global distribution of 5423 islets depending on their perimeter and area. The dotted trend line of panel L uses a polynomial order 4. The straight dotted line and the arrows in semicircle in panel K and L, represent a barrier over which the clusters of islets have been observed.

Figure 2. Heat map distribution of the pancreatic islets by their number and surface area.

(A) Global heat map representing the overlapped distributions of panel C (sum of all densities from B1 to B4). The yellow areas represent higher densities of islets while the red color represents areas of a lower density, (B) total islet area by slice (B1–4), (C) heat map which indicates the surface area occupied by islets, (D) heat map representing the islet density in sections B1–B4. The yellow areas represent higher densities of islets while the blue color represents areas of a lower density, (E) the total number of islets in each section, namely B1–B4, (F) global heat map representing the overlapped distributions from panel D (sum of all surface areas from B1–4). The yellow areas represent a higher surface occupancy by islets while the red color indicates a lower surface occupancy.

Figure 3. Islet proportions in the human pancreas.

(A) group of islets (top islet −6356 μm², bottom islet −54,291 μm², left islet −6700 μm²) included in the category 1000–10,000 μm² and 10,000–100,000 μm² (field of view 20X), (B) islet example (41,708 μm²) included in the category of 10,000 μm²–100,000 μm² (field of view 20X), (C) sample of islets (top islet −386 μm², bottom islet −8814 μm²) included in the category <1000 μm² and 1000–10,000 μm² (field of view 40X), (D) islet (20,368 μm²) belonging in the catgory 10,000–100,000 μm² (field of view 20X), (E) example of islet (6282 μm²) included in the category 1000–10,000 μm² (field of view 40X), (F) islet sample (8805 μm²) included in the category 10,000–100,000 μm² (field of view 40X), (G) group of islets (top-left islet −14,930 μm², bottom islet −136 μm², bottom-right islet −8402 μm²) ranging from 1000-10,000 μm² to 10,000–100,000 μm² (field of view 20X), (H) example of islet (29,975 μm²) included in the category 10,000–100,000 μm² (field of view 20X), (I) islet percentage by size, (K) mean islet area (dark-gray on right axis) and mean islet perimeter (light-gray on left axis) by slice (B1–4).

Figure 4. Islet clusters and the status quo inflammatory process of the peripancreatic adipose tissue.

(A) relative location of the islet cluster on B2(P14) slide (neck of the pancreas). The panel also shows the relative location of the neck of the pancreas and the heat map derived from it, which further indicates the surface area occupied by islets. (B) islet cluster boundaries (black dotted line) on B2(P14) slide (field of view 4x), (C) window in to the lower part of the islet cluster (red dotted line), (D) close view of the islets inside the cluster (field of view 20x), (E) lymphoid organized tissue inside the peripancreatic adipose tissue, taken from the head slice of the pancreas (field of view 10x). The reddish stain on the left represents a processing error. (F) inflammatory process captured on a blood vessel taken from the peripancreatic adipose tissue of the tail slice of the pancreas (field of view 20x). The blood vessel is filled with red blood cells and inflammatory cells (neutrophils, lymphocytes, eosinophils).

Figure 5. A three dimensional distribution of islets within the human pancreas.

(A) rotational view of the islet landscapes on sectons B1–4, representing the density of islets. Yellow areas represent the maximum density of islets (233 islets) and blue areas represent the minimum density of islets. (B) the 3D islet route through the human pancreas, from the head section to the tail section of the pancreas, (C) a rotational view of the global islet distribution (all B1–4 slices combined), representing the density of islets through the human pancreas, (D) a rotational view of the surface areas occupied by islets through the human pancreas. Light gray areas represent the maximum density/surface area of islets from all B1–4 slices and dark gray areas represent the minimum density/surface area of islets from all B1–4 slices.

Figure 6. The 3D routes of human pancreatic islets.

(A) the highest density peaks recorded from the superposition of eight heat map distributions, namely the B1–4 distribution of islets by number and the B1–4 distribution of islets by surface area. Depending on the slice, a distinct color has been assigned to each set of data points. (B) an overlay of the B1-B2, B2-B3 and B3-B4 metric spaces, (C) clusters indicating the closest data points between neighboring slices. The colors change their meaning to accommodate an identity to each cluster. (D) a 2D evaluation of the islet routes according to the clusters shown in panel C. (F) a 3D evaluation of the islet routes. In order to provide an identity to each islet route, the colors change their meaning once again.