Assessment of Human Pancreatic Islet Architecture and Composition by Laser Scanning Confocal Microscopy

Abstract

S U M M A R YThe recent success of pancreatic islet transplantation has generated considerable enthusiasm. To better understand the quality and characteristics of human islets used for transplantation, we performed detailed analysis of islet architecture and composition using confocal laser scanning microscopy. Human islets from six separate isolations provided by three different islet isolation centers were compared with isolated mouse and non-human primate islets. As expected from histological sections of murine pancreas, in isolated murine islets ␣ and ␦ cells resided at the periphery of the ␤ -cell core. However, human islets were markedly different in that ␣ , ␤ , and ␦ cells were dispersed throughout the islet. This pattern of cell distribution was present in all human islet preparations and islets of various sizes and was also seen in histological sections of human pancreas. The architecture of isolated non-human primate islets was very similar to that of human islets. Using an image analysis program, we calculated the volume of ␣ , ␤ , and ␦ cells. In contrast to murine islets, we found that populations of islet cell types varied considerably in human islets. The results indicate that human islets not only are quite heterogeneous in terms of cell composition but also have a substantially different architecture from widely studied murine islets.

Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in β-cells from mice and humans

“…(Brissova et al, 2005;Braun et al, 2008)]. Mathematical modeling of electrical acitivity (Pedersen, 2010a) and exocytosis (subsection 3.3) in β-cells are beginning to take these differences into account.…”

“…Human β-cells differ from their rodent counterparts in several aspects, for example with respect to their organization within the pancreatic islets (Brissova et al, 2005;Cabrera et al, 2006;Bosco et al, 2010) and the expression, regulation and role of various ion channels (Pressel and Misler, 1990;Barnett et al, 1995;Braun et al, 2008). The kinetics and control of exocytosis are also different.…”

Pancreas organogenesis: From bud to plexus to gland

“…There are also comparative studies showing the differential distribution of endocrine cells amongst the various regions of the human and mouse pancreas. Greater numbers of PP cells are located in the human head region, with more a-cells and b-cells in the neck, body, and tail regions (Stefan et al, 1982;Brissova et al, 2005). Mouse islets comprise $75% b-cells, $20% a-cells, and $5% other endocrine cells; while human islets contain $50% b-cells, $40% a-cells, $10% dcells, and a few PP cells (Brissova et al, 2005).…”

“…Greater numbers of PP cells are located in the human head region, with more a-cells and b-cells in the neck, body, and tail regions (Stefan et al, 1982;Brissova et al, 2005). Mouse islets comprise $75% b-cells, $20% a-cells, and $5% other endocrine cells; while human islets contain $50% b-cells, $40% a-cells, $10% dcells, and a few PP cells (Brissova et al, 2005). The importance of these differences is still unclear, and any relevance to endocrine cell function and glucose/energy metabolism requires further detailed analysis.…”

Ghrelin-producing epsilon cells in the developing and adult human pancreas

“…The alpha cells synthesise glucagon, beta cells synthesise insulin, delta cells synthesise somatostatin and pancreatic polypeptide (PP) cells synthesise PP [1][2][3]. A few years ago, a fifth mammalian islet cell type, the ghrelin-producing epsilon cell, was described [4,5].…”