Rheb1 signaling and the fate of pancreatic β cells: Toward a new frontier in diabetes therapy

Abstract

A recent study in the World Journal of Diabetes by Yang et al explored how Rheb1 signaling influenced pancreatic β 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 β cell biology, providing critical insight into the role of Rheb1 in β 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 β cell growth and insulin secretory function, aligning with evidence that β cell-specific Rheb1 deletion impairs β cell mass and glucose-stimulated insulin secretion. The commentary highlighted how modulating this pathway could preserve or restore the β cell population in diabetes while cautioning about potential off-target effects (e.g. in α cells). Targeting Rheb1 signaling represents a promising new frontier in diabetes therapy to enhance β 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.

Keywords: Pancreatic β cell fate; Rheb1 signaling; mTOR pathway; Diabetes therapy; Β cell survival

Core Tip: Rheb1 is a critical regulator of pancreatic β cell survival and insulin secretion, acting through the mechanistic target of rapamycin complex 1 pathway to support β cell mass and function. This invited commentary evaluated how Rheb1-driven signaling modulates β cell fate and assesses its promise as a therapeutic target in diabetes. While enhancing Rheb1 activity could preserve or expand functional β cell mass, careful modulation is required to avoid unintended effects such as α cell overactivity. Understanding the dualistic nature of Rheb1 signaling in islet cell populations will be key to harnessing this pathway for future diabetes treatments.