Pancreatic β-cell failure,clinical implications,and therapeutic strategies in type 2 diabetes  

作　　者：Daxin Cui Xingrong Feng Siman Lei Hongmei Zhang Wanxin Hu Shanshan Yang Xiaoqian Yu Zhiguang Su 

机构地区：[1]Molecular Medicine Research Center and Department of Endocrinology and Metabolism,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China [2]State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China [3]Clinical Translational Innovation Center,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China

出　　处：《Chinese Medical Journal》2024年第7期791-805,共15页中华医学杂志（英文版）

基　　金：National Natural Science Foundation of China(Nos.82270846 and 81770814);Sichuan Science and Technology Program(No.2023JDRC0095);National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University(No.Z20201010)

摘　　要：Pancreaticβ-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes(T2D).Reserving insulin-producingβ-cells and hence restoring insulin production are gaining attention in translational diabetes research,andβ-cell replenishment has been the main focus for diabetes treatment.Significant findings inβ-cell proliferation,transdifferentiation,pluripotent stem cell differentiation,and associated small molecules have served as promising strategies to regenerateβ-cells.In this review,we summarize current knowledge on the mechanisms implicated inβ-cell dynamic processes under physiological and diabetic conditions,in which genetic factors,age-related alterations,metabolic stresses,and compromised identity are critical factors contributing toβ-cell failure in T2D.The article also focuses on recent advances in therapeutic strategies for diabetes treatment by promotingβ-cell proliferation,inducing non-β-cell transdifferentiation,and reprograming stem cell differentiation.Although a significant challenge remains for each of these strategies,the recognition of the mechanisms responsible forβ-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenousβ-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes.

关 键 词：Pancreaticβ-cell regeneration Diabetes INSULIN DEDIFFERENTIATION TRANSDIFFERENTIATION Stem cell 

分 类 号：R587.1[医药卫生—内分泌]