Nrf2 Gene Expression, β Cell Oxidative Stress

Tsehay Abebe, Lindsey Bogachus, Adithya Krishna Vegaraju, R Paul Robertson
Journal of the Endocrine Society, Volume 7, Issue 3, March 2023, bvac178
https://doi.org/10.1210/jendso/bvac178

Abstract

Context

Chronic exposure of pancreatic islets to elevated glucose levels causes progressive declines in β cell Pdx-1 and insulin gene expression, and glucose-induced insulin secretion. This has been shown to be associated with excessive islet reactive oxygen species and consequent damage to β cell function, a process termed glucose toxicity. In short-term rodent in vivo studies, Nrf2 (Kelch-like ECH-associated protein 1:nuclear factor erythroid-derived-2 related factor complex) has been shown to play a central role in defending β cells from oxidative damage via activation of antioxidant gene expression.

Objective

The current studies were primarily designed to examine the behavior of Nrf2 gene expression during longer-term exposure of β cells to glucose toxicity.

Methods and Results

We provide evidence that gene expression of Nrf2 in HIT-T15 cells, an insulin-secreting β-cell line, undergoes a biphasic response characterized by an initial decrease followed by increased expression during prolonged culturing of these cells in a physiologic (0.8 mM) but not a supraphysiologic (16.0 mM) glucose concentration. This was associated with a slight rise in HO-1 gene expression. Pdx-1 and insulin mRNA levels also decreased but then stabilized in late passages of cells that had been cultured in low glucose concentrations.

Conclusion

These complex events support the concept that Nrf2 gene expression plays an important regulatory role in defending β cells during prolonged exposure to oxidative stress.

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