A loss of function variant in <i>SLC30A8/ZnT8</i> drives proteomic changes associated with lowered apoptosis in human stem cell-derived islets

Aims and hypothesis: depletion on cell survival and function. Methods: ) dynamics were measured using the intracellular probe (Cal590) and insulin secretion by homogenous time-resolved fluorescence. Transcriptomic profiling was performed by bulk mRNA sequencing and proteomics by liquid chromatography-tandem mass spectrometry. Results: depletion. Conclusion and interpretation: signaling and insulin secretion, supported by a structural remodeling and the downregulation of apoptosis and cellular stress. These findings highlight the therapeutic potential of targeting ZnT8 in type 2 diabetes and support its relevance for further improving cell-based therapies. Research in Context: mutation carriers, may be helpful in some populations to lower diabetes risk.