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

• Published in: Journal of advanced research Vol. 62; pp. 71 - 89
• Main Authors: Niu, Fanglin, Liu, Wenxuan, Ren, Yuanyuan, Tian, Ye, Shi, Wenzhen, Li, Man, Li, Yujia, Xiong, Yuyan, Qian, Lu
• Format: Journal Article
• Language: English
• Published: Egypt Elsevier B.V 01-08-2024; Elsevier
• Subjects: Animals; Basic and Biological Science; Dedifferentiation; Diabetes mellitus; Diabetes Mellitus - metabolism; Diabetes Mellitus - therapy; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - therapy; Diabetes Mellitus, Type 2 - metabolism; Endoplasmic Reticulum Stress; Humans; Insulin-Secreting Cells - metabolism; Islet β-cells; Oxidative Stress; Signal Transduction; Trans-differentiation; β-cells failure; β-cells neogenesis; T1DM; FFA; BETA2; GWAS; JNK; CDK; C/EBP-β; FGF4; NF-κB; IFN-γ; PI3K; RNS; HBP; STZ; CHOP; SOX9; Islet β-cells; ESCs; GLP-1 RAs; TRAF2; IL-1β; ER; p38 MAPK; IL-6; eIF2aZ; GSIS; ROS; GABA; Trans-differentiation; AMPK; NGN3; ATF6; mTORC1; ATF3; ATF4; ERK; T2DM; β-cells failure; DPP-IV; PKC-δ; GSK-3; PERK; Mef2d; FOXO1; UDP-GlcNAc; Nrf2; IRE1; NLRP3; O-GlcNAcylation; HES1; NADP; ASCs; XBP1; GLP-1; Diabetes mellitus; PDX1; OGA; β-cells neogenesis; AKT; MAFA; Dedifferentiation; Bax; OGT
• ISSN: 2090-1232; 2090-1224; 2090-1224
• DOI: 10.1016/j.jare.2023.10.008

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•Progressive β-cell failure is central to the pathophysiological mechanisms of insulin-deficient diabetes mellitus.•The molecular mechanisms of β-cell failure engage multiple biological processes such as genetic susceptibility, endoplasmic reticulum (ER) stress, oxidative stress, islet inflammation, and protein modifications linked to multiple signaling pathways.•The potential source of β-cell neogenesis include stimulating existing β-cell proliferation, promoting stem cell differentiation, and directing trans-differentiation of non-β-cells in the endocrine pancreas (α-cells, δ-cells, and γ-cells) and exocrine pancreas (acinar cells and ductal cells), as well as other tissues and cells such as the liver, pancreas, intestine, and endocrine progenitor-like cells.
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).
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.
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.