β-cell neogenesis: A rising star to rescue diabetes mellitus

Fanglin Niu; Wenxuan Liu; Yuanyuan Ren; Ye Tian; Wenzhen Shi; Man Li; Yujia Li; Yuyan Xiong; Lu Qian

doi:10.1016/j.jare.2023.10.008

β-cell neogenesis: A rising star to rescue diabetes mellitus

J Adv Res. 2023 Oct 13:S2090-1232(23)00312-0. doi: 10.1016/j.jare.2023.10.008. Online ahead of print.

Authors

Fanglin Niu¹, Wenxuan Liu¹, Yuanyuan Ren¹, Ye Tian², Wenzhen Shi³, Man Li⁴, Yujia Li⁴, Yuyan Xiong¹, Lu Qian⁵

Affiliations

¹ Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, the Affiliated Hospital of Northwest University, Xi'an No.3 Hospital, Xi'an, Shaanxi, PR China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, China.
² Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, the Affiliated Hospital of Northwest University, Xi'an No.3 Hospital, Xi'an, Shaanxi, PR China; Department of Neurology, Affiliated Hospital of Northwest University, Xi'an No.3 Hospital, Xi'an, Shaanxi, China.
³ Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, the Affiliated Hospital of Northwest University, Xi'an No.3 Hospital, Xi'an, Shaanxi, PR China; Medical Research Center, the affiliated Hospital of Northwest University, Xi'an No.3 Hospital, Xi'an, Shaanxi, China.
⁴ Department of Endocrinology, the Affiliated Hospital of Northwest University, Xi'an No.3 Hospital, Xi'an, Shaanxi, China.
⁵ Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, the Affiliated Hospital of Northwest University, Xi'an No.3 Hospital, Xi'an, Shaanxi, PR China; Department of Endocrinology, the Affiliated Hospital of Northwest University, Xi'an No.3 Hospital, Xi'an, Shaanxi, China.

PMID: 37839502
DOI: 10.1016/j.jare.2023.10.008

Abstract

Background: Diabetes Mellitus (DM), a chronic metabolic disease characterized by elevated blood glucose, is caused by various degrees of insulin resistance and dysfunctional insulin secretion, resulting in hyperglycemia. The loss and failure of functional β-cells are key mechanisms resulting in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).

Aim of review: Elucidating the underlying mechanisms of β-cell failure, and exploring approaches for β-cell neogenesis to reverse β-cell dysfunction may provide novel strategies for DM therapy.

Key scientific concepts of review: Emerging studies reveal that genetic susceptibility, endoplasmic reticulum (ER) stress, oxidative stress, islet inflammation, and protein modification linked to multiple signaling pathways contribute to DM pathogenesis. Over the past few years, replenishing functional β-cell by β-cell neogenesis to restore the number and function of pancreatic β-cells has remarkably exhibited a promising therapeutic approach for DM therapy. In this review, we provide a comprehensive overview of the underlying mechanisms of β-cell failure in DM, highlight the effective approaches for β-cell neogenesis, as well as discuss the current clinical and preclinical agents research advances of β-cell neogenesis. Insights into the challenges of translating β-cell neogenesis into clinical application for DM treatment are also offered.

Keywords: Dedifferentiation; Diabetes mellitus; Islet β-cells; Trans-differentiation; β-cells failure; β-cells neogenesis.

Publication types

Review