Scientific article
Open access

Mitochondrial carriers regulating insulin secretion profiled in human islets upon metabolic stress

Published inBiomolecules, vol. 10, no. 11, 1543
Publication date2020

Chronic exposure of β-cells to nutrient-rich metabolic stress impairs mitochondrial metabolism and its coupling to insulin secretion. We exposed isolated human islets to different metabolic stresses for 3 days: 0.4 mM oleate or 0.4 mM palmitate at physiological 5.5 mM glucose (lipotoxicity), high 25 mM glucose (glucotoxicity), and high 25 mM glucose combined with 0.4 mM oleate and/or palmitate (glucolipotoxicity). Then, we profiled the mitochondrial carriers and associated genes with RNA-Seq. Diabetogenic conditions, and in particular glucotoxicity, increased expression of several mitochondrial solute carriers in human islets, such as the malate carrier DIC, the α-ketoglutarate-malate exchanger OGC, and the glutamate carrier GC1. Glucotoxicity also induced a general upregulation of the electron transport chain machinery, while palmitate largely counteracted this effect. Expression of different components of the TOM/TIM mitochondrial protein import system was increased by glucotoxicity, whereas glucolipotoxicity strongly upregulated its receptor subunit TOM70. Expression of the mitochondrial calcium uniporter MCU was essentially preserved by metabolic stresses. However, glucotoxicity altered expression of regulatory elements of calcium influx as well as the Na+/Ca2+ exchanger NCLX, which mediates calcium efflux. Overall, the expression profile of mitochondrial carriers and associated genes was modified by the different metabolic stresses exhibiting nutrient-specific signatures.

  • Swiss National Science Foundation - 166625
  • Autre - Hjelt Diabetes Foundation
Citation (ISO format)
JIMÉNEZ-SÁNCHEZ, Cecilia, BRUN, Thierry, MAECHLER, Pierre. Mitochondrial carriers regulating insulin secretion profiled in human islets upon metabolic stress. In: Biomolecules, 2020, vol. 10, n° 11, p. 1543. doi: 10.3390/biom10111543
Main files (1)
Article (Published version)
Secondary files (1)
ISSN of the journal2218-273X

Technical informations

Creation11/27/2020 11:15:00 AM
First validation11/27/2020 11:15:00 AM
Update time03/15/2023 11:36:25 PM
Status update03/15/2023 11:36:24 PM
Last indexation02/12/2024 11:59:21 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack