Karimkhani, Hadi2026-01-152026-01-1520251948-935810.4239/wjd.v16.i12.108609https://doi.org/10.4239/wjd.v16.i12.108609https://hdl.handle.net/20.500.14517/8704A recent study in the World Journal of Diabetes by Yang et al explored how Rheb1 signaling influenced pancreatic beta cell fate and its potential as a therapeutic target. This invited commentary by a senior diabetes researcher discussed the findings of Yang et al in the context of current knowledge on beta cell biology, providing critical insight into the role of Rheb1 in beta cell survival and function and the prospects for diabetes treatment. Key outcomes of the study were interpreted alongside established literature on Rheb1- mechanistic target of rapamycin signaling in islet cells. Rheb1 emerges as a pivotal regulator of beta cell growth and insulin secretory function, aligning with evidence that beta cell-specific Rheb1 deletion impairs beta cell mass and glucose-stimulated insulin secretion. The commentary highlighted how modulating this pathway could preserve or restore the beta cell population in diabetes while cautioning about potential off-target effects (e.g. in alpha cells). Targeting Rheb1 signaling represents a promising new frontier in diabetes therapy to enhance beta cell resilience; however, a balanced approach addressing both its benefits and risks is essential. This letter discussed the scientific implications and future research directions needed to translate Rheb1 modulation into clinical application for diabetes.eninfo:eu-repo/semantics/openAccessPancreatic Beta Cell FateRheb1 SignalingmTOR PathwayDiabetes TherapyBeta Cell SurvivalLetterQ1N/A1612WOS:00165147440002241480603