NIH R01 · 2025
Metabolic crosstalks in regulation of beta-cell stress response and adaptation
Abstract Glucose metabolism generates important signals that regulate several facets of β-cell health, including insulin secretion, proliferation, survival, and differentiation. We have found that the TCA cycle enzyme pyruvate carboxylase (PC), which promotes metabolic signals that regulate insulin secretion, has previously unappreciated roles in β-cell stress mitigation by promoting urea cycle activity and de novo glutathione (GSH) synthesis. These PC-directed pathways can promote a dual defense mechanism, whereby nitric oxide (NO) synthesis from arginine is reduced as arginine is utilized for ureagenesis and antioxidant capacity is increased by de novo GSH synthesis in the face of…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.