The ductal origin of structural and functional heterogeneity between pancreatic islets |
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Authors: | Claudia Merkwitz Orest W Blaschuk Angela Schulz Paul Lochhead Jaroslawna Meister Angela Ehrlich Albert M Ricken |
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Institution: | 1. Institute of Anatomy, Faculty of Medicine, University of Leipzig, Liebigstraße 13, 04103 Leipzig, Germany;2. Division of Urology, Department of Surgery, McGill University, Urology Research Laboratories, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC H3A 1A1, Canada;3. IFB Adiposity Diseases and Institute of Biochemistry, Faculty of Medicine, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany;4. Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom |
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Abstract: | Islets form in the pancreas after the first endocrine cells have arisen as either single cells or small cell clusters in the epithelial cords. These cords constitute the developing pancreas in one of its earliest recognizable stages. Islet formation begins at the time the cords transform into a branching ductal system, continues while the ductal system expands, and finally stops before the exocrine tissue of ducts and acini reaches its final expansion. Thus, islets continuously arise from founder cells located in the branching and ramifying ducts. Islets arising from proximal duct cells locate between the exocrine lobules, develop strong autonomic and sensory innervations, and pass their blood to efferent veins (insulo-venous efferent system). Islets arising from cells of more distal ducts locate within the exocrine lobules, respond to nerve impulses ending at neighbouring blood vessels, and pass their blood to the surrounding acini (insulo-acinar portal system). Consequently, the section of the ductal system from which an islet arises determines to a large extent its future neighbouring tissue, architecture, properties, and functions. We note that islets interlobular in position are frequently found in rodents (rats and mice), whereas intralobularly-located, peripheral duct islets prevail in humans and cattle. Also, we expound on bovine foetal Laguesse islets as a prominent foetal type of type 1 interlobular neuro-insular complexes, similar to neuro-insular associations frequently found in rodents. Finally, we consider the probable physiological and pathophysiological implications of the different islet positions within and between species. |
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Keywords: | CK cytokeratin E-cadherin epithelial-cadherin ed embryonic day EP-CAM epithelial cell adhesion molecule ew embryonic week GCG glucagon GHRL ghrelin GLP-1 glucagon-like peptide-1 HE haematoxylin and eosin HNF1β hepatocyte nuclear factor 1 beta INS insulin N-cadherin neural-cadherin N-CAM neural cell adhesion molecule NGN-3 neurogenin-3 NIC neuro-insular complex PC prohormone convertase pcd post coitum day pp postpartum PHHI persistent hyperinsulinaemic hypoglycaemia of infancy PPY pancreatic polypeptide PDX-1 pancreatic and duodenal homeobox-1 R-cadherin retinal-cadherin SOX9 SRY (sex-determining region Y)-box 9 SST somatostatin T1D type 1 diabetes TGF-β transforming growth factor-ß |
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