Summary of the study.

Redox signaling is involved in insulin secretion on glucose induction in pancreatic β cells (NADPH oxidase isoform 4 [NOX4] is the major player), whereas oxidative stress in β cells leads to the development of type 2 diabetes. Sustained activation of NOX4 in β cells by chronic overnutrition induces the inflammasome and IL-1β production, leading to macrophage activation and local inflammation. Thus, βNOX4−/− mice do not develop chronic inflammation on HFD, suggesting the role of sustained NOX4 activation in diabetes development. Redox regulation in β cells is an important player in their physiology and NOX4 might be a potential pharmacological target during chronic nutritional overload.