Multi‐Omics Integration Identifies the <scp>CBS</scp> – <scp>CTH</scp> – <scp>GSH</scp> Axis as a Critical Regulator of β‐Cell Ferroptosis in Type 2 Diabetes

accumulation, and shifted ferroptosis markers toward an anti-ferroptotic profile, accompanied by improved β-cell functional gene expression. Notably, inhibition of GSH synthesis largely abolished the protective effects of CBS, indicating that the anti-ferroptotic function is GSH dependent. Mechanistically, cystathionine γ-lyase (CTH) was identified as an essential coregulator of CBS. Disruption of CTH greatly weakened CBS-driven improvements in GSH maintenance, iron-redox homeostasis, and β-cell function, establishing a functional CBS-CTH-GSH axis. In summary, our findings identify that CBS can protect β-cells from ferroptotic injury and functional decline under glucotoxic stress and highlight the CBS-CTH-GSH axis as a promising β-cell-targeted intervention point for delaying or preventing T2DM progression.