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

Figure 1

Glucolipotoxicity impairs insulin release and alters acute, glucose-induced changes in redox balance. (a–c) Mouse islet cells were cultured in control medium (10 mmol/L glucose) or in glucolipotoxic culture medium (100 μmol/L palmitate and 25 mmol/L glucose) for up to 48 h. Thereafter, they were stimulated with bath solution supplemented with either 0.5 or 15 mmol/L glucose for 1 h and changes in fluorescence of DHE_ox ((a), indicative of superoxide anion formation), DCF ((b), indicative of a more oxidized redox status), and BES-H₂O₂ ((c), indicative of H₂O₂ accumulation) were determined. (d) Insulin release of murine islets was measured in response to 3 and 15 mmol/L glucose (1 h steady-state incubation) after 2 or 48 h in culture medium with 100 μmol/L palmitate and 25 mmol/L glucose vs. control (10 mmol/L glucose). In (a) and (b), representative images are shown on the left. Numbers in the graph indicate the number of islet cells ((a–c): 0,5/15 mmol/L glucose) or independent preparations (d). , , and ; 15 vs. 0.5 or 3 mmol/L glucose, n. s.: not significant.

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