Overview
- Peer-reviewed work in Nature Metabolism reports that cutting NADPH production raises oxidative stress and speeds the growth of precancerous pancreatic lesions.
- The study flagged two NADPH-making enzymes, G6PD and ME1, as active in metaplasia and found that lowering either one increased acinar-to-ductal metaplasia and PanIN lesions in KRAS mouse models.
- Antioxidant treatment blunted the surge in lesions, with glutathione helping cells in dishes and N-acetyl cysteine helping mice in vivo.
- Only the loss of ME1 pushed lesions to full pancreatic ductal adenocarcinoma in the models, while G6PD loss did not cause that step.
- Findings were echoed in human pancreatic tissue, and the team says enzyme levels or related metabolites could guide early risk tests and interception trials, with plans to probe other NADPH regulators and patient genetic variants next.