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Role of LRH-1/NR5A2 in islet physiology and pathophysiology

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Defense Thèse de doctorat : Univ. Genève, 2010 - Sc. 4260 - 2010/10/12
Abstract The nuclear receptor Liver Receptor Homolog-1 (LRH-1) plays a key role in several biological processes. The correlative association between LRH-1 function induced by estrogens and the protective role of the hormone on pancreatic insulin-secreting ß-cells led us to investigate the potential implication of LRH-1 in islet ß-cell physiology. We demonstrate that LRH-1 is expressed in ß-cells and that transcript levels are modulated by 17ß-estradiol through the ERa signalling pathway. Adenoviral-mediated overexpression of LRH-1 in human islets did not alter proliferation but conferred protection against cytokines and streptozotocin-induced apoptosis. More importantly, incubation of human islets with an agonist of LRH-1 (BL001) also protected islets against cell death caused by cytokines and streptozotocin. BL001 also increased overall ß-cell performance in islets isolated from Type 2 diabetic donors. Our results indicate that LRH-1 could be an attractive target for stimulating islet survival and performance in diabetic patients.
Keywords LRH-1/NR5A2Islet physiologyPathophysiology
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URN: urn:nbn:ch:unige-125865
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BAQUIE, Mathurin. Role of LRH-1/NR5A2 in islet physiology and pathophysiology. Université de Genève. Thèse, 2010. https://archive-ouverte.unige.ch/unige:12586

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Deposited on : 2010-11-24

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