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In the TME, despite various ammonia clearance mechanisms, rapidly proliferating cells, particularly tumor and immune effector cells, have a heightened demand for α-KG derived from glutamine breakdown to fuel the TCA cycle, leading to substantial free ammonia production (103)

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It formally characterises DSIP as “a still unresolved riddle” — acknowledging that no specific DSIP receptor has been confirmed, that the existence of DSIP-like endogenous peptides distinct from DSIP itself may account for a substantial proportion of DSIP-like immunoreactivity data, and that the most robust SWS-promoting activity in rodent studies has been demonstrated for synthetic DSIP structural analogues rather than native DSIP itself