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Mechanisms and functions of glutamate transport in betacell mitochondria for the control of insulin secretion

Defense Thèse de doctorat : Univ. Genève, 2009 - Sc. 4053 - 2009/01/21
Abstract The mitochondrial glutamate carrier 1 (GC1) was previously cloned from human brain cDNA and showed high levels of expression in the whole pancreas. According to the role that glutamate might play in ß cells as an additive factor in glucose stimulated insulin secretion, it was of interest to determine if GC1 was expressed in insulin secreting cell lines as well as primary cells and to assess whether GC1 suppression would affect glucose stimulated insulin secretion. In the course of this study, we have demonstrated GC1 expression in pancreatic ß cells. The downregulation of GC1 had little impact on mitochondrial proton gradient although it promoted a decrease in glucose evoked insulin secretion at stimulatory glucose concentration. This defect in the secretory response was restored upon provision of cell permeant methyl-glutamate. In conclusion, we have shown that GC1 is necessary for the full development of glucose induced insulin secretion, although the exact site for glutamate action is currently unknown. Further investigation should delineate the specific role of GC1 in insulin release.
Keywords GlutamateBeta-cellInsulin secretionTransporter
URN: urn:nbn:ch:unige-22400
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Research group Mitochondries et métabolisme énergétique (671)
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CASIMIR, Marina Shamini. Mechanisms and functions of glutamate transport in betacell mitochondria for the control of insulin secretion. Université de Genève. Thèse, 2009. doi: 10.13097/archive-ouverte/unige:2240 https://archive-ouverte.unige.ch/unige:2240

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Deposited on : 2009-07-21

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