Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jan 26, 2021; 13(1): 64-77
Published online Jan 26, 2021. doi: 10.4252/wjsc.v13.i1.64
Pancreatic β cell regeneration induced by clinical and preclinical agents
Kang-Li Wang, Ming Tao, Tian-Jiao Wei, Rui Wei
Kang-Li Wang, Tian-Jiao Wei, Rui Wei, Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, China
Ming Tao, Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
Author contributions: Wang KL and Tao M contributed equally to this work; Wang KL, Tao M, and Wei TJ collected the supportive literature and drafted the manuscript; Wei R conceived the manuscript, reviewed the literature, and revised and proofread the manuscript; all authors have read and approved the final manuscript.
Supported by the National Key Research and Development Program of China, No. 2016YFA0100501; the National Natural Science Foundation of China, No. 81770768 and No. 81970671; and the Natural Science Foundation of Beijing, No. 7192225.
Conflict-of-interest statement: The author declares no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Rui Wei, MD, PhD, Department of Endocrinology and Metabolism, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing 100191, China.
Received: June 29, 2020
Peer-review started: June 29, 2020
First decision: October 21, 2020
Revised: November 16, 2020
Accepted: November 28, 2020
Article in press: November 28, 2020
Published online: January 26, 2021

Diabetes, one of the most common chronic diseases in the modern world, has pancreatic β cell deficiency as a major part of its pathophysiological mechanism. Pancreatic regeneration is a potential therapeutic strategy for the recovery of β cell loss. However, endocrine islets have limited regenerative capacity, especially in adult humans. Almost all hypoglycemic drugs can protect β cells by inhibiting β cell apoptosis and dedifferentiation via correction of hyperglycemia and amelioration of the consequent inflammation and oxidative stress. Several agents, including glucagon-like peptide-1 and γ-aminobutyric acid, have been shown to promote β cell proliferation, which is considered the main source of the regenerated β cells in adult rodents, but with less clarity in humans. Pancreatic progenitor cells might exist and be activated under particular circumstances. Artemisinins and γ-aminobutyric acid can induce α-to-β cell conversion, although some disputes exist. Intestinal endocrine progenitors can transdeterminate into insulin-producing cells in the gut after FoxO1 deletion, and pharmacological research into FoxO1 inhibition is ongoing. Other cells, including pancreatic acinar cells, can transdifferentiate into β cells, and clinical and preclinical strategies are currently underway. In this review, we summarize the clinical and preclinical agents used in different approaches for β cell regeneration and make some suggestions regarding future perspectives for clinical application.

Keywords: β cell regeneration, β cell dedifferentiation, Cell proliferation, Pancreatic progenitors, α-to-β cell transdifferentiation, Enteroendocrine progenitor cells

Core Tip: Pancreatic regeneration is a potential therapeutic strategy for β cell recovery in diabetes. Previous studies have focused on the various cell types and different strategies for islet regeneration. However, how far this is from clinical application has not been fully elucidated. In this review, we focus on the clinical and preclinical agents used in different approaches. The clinical potential and disadvantages of the various approaches are discussed, and some suggestions are made for future perspectives.