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

Sep 28, 2026

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 in the context of current β cell biology, emphasizing Rheb1’s role in β cell survival and function. The letter interpreted key outcomes alongside Rheb1–mTOR mechanistic target evidence in islet cells, highlighting impaired β cell mass and glucose-stimulated insulin secretion with β cell-specific Rheb1 deletion. It considers pathway modulation to preserve β cells in diabetes while noting possible off-target effects, and outlines scientific implications and future research needed for clinical translation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages6

Reading Time15 min

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Abstract

Core Tip

Citation

Rheb1 signaling in β cell function and survival

Rheb1-mTORC1 nutrient-sensing axis

| W | J | D | World Journal of
Diabetes | | --- | --- | --- | --- | Submit a Manuscript: [https://www.f6publishing.com](https://www.f6publishing.com) World J Diabetes 2025 December 15; 16(12): 108609 DOI: 10.4239/wjd.v16.i12.108609 ISSN 1948-9358 (online) LETTER TO THE EDITOR Rheb1 signaling and the fate of pancreatic β cells: Toward a new frontier in diabetes therapy Hadi Karimkhani Specialty type: Endocrinology and metabolism Provenance and peer review: Invited article; Externally peer reviewed. Peer-review model: Single blind Peer-review report’s classification Scientific Quality: Grade A, Grade B, Grade B, Grade C Novelty: Grade A, Grade B, Grade B, Grade D Creativity or Innovation: Grade A, Grade B, Grade C, Grade D Scientific Significance: Grade B, Grade B, Grade B, Grade D P-Reviewer: He YL, Chief Physician, China; Li Z, Academic Fellow, Post Doctoral Researcher, China; Tian LB, PhD, Assistant Professor, China Received: April 18, 2025 Revised: August 13, 2025 Accepted: October 23, 2025 Published online: December 15, 2025 Processing time: 241 Days and 11.9 Hours Hadi Karimkhani, Medical Biochemistry, İstanbul Okan University, İstanbul 34959, Tuzla, Türkiye Corresponding author: Hadi Karimkhani, PhD, Assistant Professor, Medical Biochemistry,İstanbul Okan University, Tepeören Mahallesi Tuzla Kampüsü, İstanbul 34959, Tuzla, Türkiye. [drhadi.h@gmail.com](drhadi.h@gmail.com) Abstract A recent study in the World Journal ofDiabetes 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. Key Words: Pancreatic β cell fate; Rheb1 signaling; mTOR pathway; Diabetes therapy; Β cell survival ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved. WJD [https://www.wjgnet.com](https://www.wjgnet.com) 1 December 15, 2025 Volume 16 Issue 12 Karimkhani H. Rheb1 signaling and β cell fate 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. Citation: Karimkhani H. Rheb1 signaling and the fate of pancreatic β cells: Toward a new frontier in diabetes therapy. World J Diabetes 2025; 16(12): 108609 URL: [https://www.wjgnet.com/1948-9358/full/v16/i12

FAQs

What role does Rheb1 play in pancreatic β cell survival and insulin secretion?

Rheb1 is described as a pivotal regulator of β cell growth and insulin secretory function, acting through the mechanistic target of rapamycin complex 1 pathway to support β cell mass and function.

How does β cell-specific deletion of Rheb1 affect diabetes-related outcomes?

The commentary reports that β cell-specific Rheb1 deletion impairs β cell mass and glucose-stimulated insulin secretion, highlighting Rheb1’s essential contribution to maintaining an adequate β cell population.

Why does the letter emphasize a balanced approach when targeting Rheb1 signaling?

Modulating Rheb1 signaling could preserve or restore the β cell population, but the letter cautions about potential off-target effects, including possible impacts on other islet cell types such as α cells.

Sep 28, 2026

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