Doctoral thesis
Open access

Role Of FFAR1 in the response of INS-1E β-cells to glucolipotoxicity

ContributorsOberhauser, Lucie
Defense date2019-03-26

Chronic exposure to elevated glucose levels and free fatty acids impairs beta-cell function, leading to insulin secretion defects and beta-cell death, potentially prompting diabetes. These effects, referred to as glucolipotoxicity, and mechanisms induced by saturated versus unsaturated fatty acids remain unclear. Here, I investigated the role of the free fatty acid receptor, FFAR1, in INS-1E β-cells chronically exposed to glucose and free fatty acids. Glucose was the main driver for β-cell dysfunction. Free fatty acids exacerbated only some of the glucotoxic effects while partially restoring glucose-stimulated insulin secretion in cells exposed to glucotoxicity. The contribution of intracellular lipids in this process was highlighted. Chronic elevated glucose strongly down-regulated Ffar1 expression in INS-1E β-cells, likely minimizing its role under glucolipotoxic condition. However, in this context, the remaining fraction of FFAR1 may contribute to the partial restoration of β-cell function, notably through the binding of secreted fatty acids from intracellular lipids turnover.

Citation (ISO format)
OBERHAUSER, Lucie. Role Of FFAR1 in the response of INS-1E β-cells to glucolipotoxicity. 2019. doi: 10.13097/archive-ouverte/unige:117296
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Creation04/30/2019 6:07:00 PM
First validation04/30/2019 6:07:00 PM
Update time03/15/2023 4:29:55 PM
Status update03/15/2023 4:29:54 PM
Last indexation09/18/2023 9:13:46 PM
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