Mitochondrial Carriers Regulating Insulin Secretion Profiled in Human Islets upon Metabolic Stress.

Biomolecules
Cecilia Jimenez-SánchezPierre Maechler

Abstract

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 ...Continue Reading

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Citations

Jun 29, 2021·Antioxidants & Redox Signaling·Petr JežekLydie Plecitá-Hlavatá
Oct 27, 2021·Physiological Reviews·Joanne F Garbincius, John W Elrod

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Methods Mentioned

BETA
RNA-Seq

Software Mentioned

Omics Visualizer
Cytoscape
STRING
Primer Express
stringApp

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