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Integrating Metabolism and Immunity | EK16


Characterizing the cystine/glutamate antiporter system xC in the context of islet function.


Jan 25, 2021 12:00am ‐ Jan 25, 2021 12:00am

Description

Characterizing the cystine/glutamate antiporter system xC in the context of islet function. Axel de Baat, Leila Rachid, Helene Mereau Adriano Fontana, Marianne Boeni-Schnetzler, Marc Donath. Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, Basel, Switzerland, and Department of Biomedicine, University of Basel, Basel, Switzerland. Hyperglycemia associated redox stress is a major contributor to the diabetes. Due to the commitment of beta cells to oxidative phosphorylation in order to function as accurate glucose sensors, beta cells are especially vulnerable to redox stress. When cells experience redox stress, the expression of glutamate cystine antiporter system xC is upregulated to increase the uptake of the sulphur amino acid cystine in exchange for glutamate. This phenomenon is especially pronounced on immune cells. Cystine is subsequently reduced and incorporated into anti-oxidants such as glutathione, these anti-oxidants are a means of crosstalk between immune and beta cells. In this project mice lacking the gene encoding the critical subunit Slc7a11 of system xC were metabolically phenotyped and have been found to exhibit reduced insulin secretion both in vitro and in vivo. Current work is focused on elucidating the mechanism and source of the impaired insulin secretion, using cre-specific expression models. This project will contribute to the understanding of cystine in islet and immune metabolism and could create a basis for redox oriented strategies to maintain beta cell mass and improve immune function in the context of diabetes.

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