title: Islet alpha-cells do not influence insulin secretion from beta-cells through cell-cell contact.
abstract: Interactions between the endocrine cells in islets of Langerhans influence their secretory function, and disruption of islet structure results in impaired insulin secretory responses to both nutrient and non-nutrient stimuli. We have previously demonstrated that insulin-secreting MIN6 cells show enhanced secretory responses when grown as islet-like structures (pseudoislets) suggesting that homotypic cell-cell interactions between beta-cells are important for normal function. We have now extended this experimental model to study the role of heterotypic interactions between insulin-expressing and glucagon-expressing cells by measuring the organization and secretory function of pseudoislets formed from MIN6 and alphaTC1 cells. The direct alpha-cell to beta-cell contact in the heterogenous MIN6/alphaTC1 pseudoislets was sufficient to enable the formation of anatomically correct islet-like structures, with a central core of MIN6 cells surrounded by a periphery of alphaTC1 cells. However, the presence of alphaTC1 cells had no detectable effect on insulin secretory responses to nutrient or non-nutrient stimuli. In contrast, exogenous glucagon enhanced insulin secretion, in accordance with a paracrine role for alpha-cell-derived glucagon in the regulation of insulin secretion rather than direct, contact-mediated effects of alpha-cells on neighbouring beta-cells.
authors: Beta Cell Development and Function Group, Division of Reproduction and Endocrinology, GKT School of Biomedical and Health Sciences, King's College London, Guy's Campus, London, SE1 1UL, UK.
authors: Helen
authors: H
authors: Brereton
authors: Melanie J
authors: MJ
authors: Carvell
authors: Shanta J
authors: SJ
authors: Persaud
authors: Peter M
authors: PM
authors: Jones
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D005934:Glucagon / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice
chemical_list: D007328:Insulin; D005934:Glucagon
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