Nrf2 Activation Protects Mouse Beta Cells from Glucolipotoxicity by Restoring Mitochondrial Function and Physiological Redox Balance

Figure 6

Activation of Nrf2 prevents the inhibitory effects of glucolipotoxicity on ATP content, glucose-induced generation of NAD(P)H, and mitochondrial function. Oltipraz (10 μmol/L) or DMF (10 or 50 μmol/L) was added to isolated murine islet cells 12-16 h before changing standard medium to glucolipotoxic medium and during glucolipotoxic culture (48 h). (a) Glucose-stimulated rise in ATP content was decreased after glucolipotoxic culture. Oltipraz protected against this. (b) Glucose-stimulated elevation of NAD(P)H autofluorescence was reduced after glucolipotoxic culture. This was completely prevented by oltipraz. A representative recording after culture in standard medium is shown on the right. (c, d) Mitochondrial membrane potential (ΔΨ_m) was determined in response to 1 h stimulation with 0.5 vs. 15 mmol/L glucose after culture in control (white and grey bars) or glucolipotoxic (black and hatched bars) medium in the presence or absence of Nrf2 activators. Mitochondria damaged by glucolipotoxicity were unresponsive to glucose (black bars). Oltipraz or DMF protected against this (hatched bars). In (c), representative recordings for control conditions are shown on the right. Numbers in bars indicate the number of independent preparations (a) or cells (b–d). and ; n. s.: not significant.

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