Unique basement membrane structure of human pancreatic islets: implications for beta-cell growth and differentiation.
Basement membranes (BMs) are an important part of the physiological microenvironment of pancreatic islet cells. In mouse islets, beta-cells interact directly with BMs of capillary endothelial cells. We have shown that in the human islets, the capillaries are surrounded by a double BM both in foetal and adult tissues. The endocrine islet cells are facing a BM that is separate from the endothelia. Laminins are the functionally most important component of BMs. The only laminin isoform present in the human endocrine islet BM is laminin-511 (previously known as laminin 10). The islet cells facing this BM have a strong and polarized expression of Lutheran glycoprotein, which is a well-known receptor for the laminin alpha 5 chain. Dispersed human islet cells adhere to purified human laminin-511 and the binding is equally effectively blocked by a soluble form of Lutheran as by antibody against integrin beta1. Our results reveal unique features of the BM structure of human islets, different from rodents. This information has potentially important implications for the generation of an optimal microenvironment for beta-cell function, proliferation and differentiation.
Biomedicum Stem Cell Center and Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. timo.otonkoski@helsinki.fi
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Otonkoski
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M
Banerjee
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O
Korsgren
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LE
Thornell
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Virtanen
D000818:Animals; D001485:Basement Membrane / Q000196:embryology / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D007515:Islets of Langerhans / Q000196:embryology / Q000378:metabolism / Q000503:physiopathology*; D007797:Laminin / Q000378:metabolism / Q000502:physiology*; D008188:Lutheran Blood-Group System / Q000378:metabolism; D051379:Mice; D010179:Pancreas / Q000196:embryology / Q000503:physiopathology*; D020033:Protein Isoforms / Q000378:metabolism; D017474:Receptors, Laminin / Q000378:metabolism
D007797:Laminin; D008188:Lutheran Blood-Group System; D020033:Protein Isoforms; D017474:Receptors, Laminin; C119013:laminin 10