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Insulin secretion from human beta cells is heterogeneous and dependent on cell-to-cell contacts

Wojtusciszyn, A. ; Armanet, M. ; Morel, P. ; Berney, T. ; Bosco, D.

In: Diabetologia, 2008, vol. 51, no. 10, p. 1843-1852

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    Titre
    • Insulin secretion from human beta cells is heterogeneous and dependent on cell-to-cell contacts
    Auteur
    • Wojtusciszyn, A.. Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, 1 rue Michel Servet, 1211, Genève-4, Switzerland
    • Armanet, M.. Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, 1 rue Michel Servet, 1211, Genève-4, Switzerland
    • Morel, P.. Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, 1 rue Michel Servet, 1211, Genève-4, Switzerland
    • Berney, T.. Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, 1 rue Michel Servet, 1211, Genève-4, Switzerland
    • Bosco, D.. Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, 1 rue Michel Servet, 1211, Genève-4, Switzerland
    Type de document
    • Postprint
    Identifiant OAI-PMH
    • oai:doc.rero.ch:313583
    Summary
    Aims/hypothesis: We assessed the heterogeneity of insulin secretion from human isolated beta cells and its regulation by cell-to-cell contacts. Methods: Insulin secretion from single and paired cells was assessed by a reverse haemolytic plaque assay. The percentage of plaque-forming cells, the mean plaque area and the total plaque development were evaluated after 1h of stimulation with different secretagogues. Results: Not all beta cells were surrounded by a haemolytic plaque under all conditions tested. A small fraction of the beta cell population (20%) secreted more than 90% and 70% of total insulin at 2.2 and 22.2mmol/l glucose, respectively. Plaque-forming cells, mean plaque area and total plaque development were increased at 12.2 and 22.2 compared with 2.2mmol/l glucose. Insulin secretion of single beta cells was similar at 12.2 and 22.2mmol/l glucose. Insulin secretion of beta cell pairs was increased compared with that of single beta cells and was higher at 22.2 than at 12.2mmol/l glucose. Insulin secretion of beta cells in contact with alpha cells was also increased compared with single beta cells, but was similar at 22.2 compared with 12.2mmol/l glucose. Delta and other non-beta cells did not increase insulin secretion of contacting beta cells compared with that of single beta cells. Differences in insulin secretion between 22.2 and 12.2mmol/l glucose were observed in murine but not in human islets. Conclusions/interpretation: Human beta cells are highly heterogeneous in terms of insulin secretion so that a small fraction of beta cells contributes to the majority of insulin secreted. Homologous and heterologous intercellular contacts have a significant impact on insulin secretion and this could be related to the particular architecture of human islets