Academic Journal
Metabolic reprogramming of pancreatic beta cells in type 2 diabetes and its therapeutic strategy.
| Title: | Metabolic reprogramming of pancreatic beta cells in type 2 diabetes and its therapeutic strategy. |
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| Authors: | Miao L; Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: 1249448953@qq.com., Miao R; Oncology Department of Integrative Medicine, China-Japan Friendship Hospital, Beijing, China. Electronic address: 20160141002@bucm.edu.cn., Yao Y; Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: gzucm2019@126.com., Fang X; Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Graduate College, Beijing University of Chinese Medicine, Beijing, China. Electronic address: 749860324@qq.com., Guan H; Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Changchun University of Chinese Medicine, Changchun, China. Electronic address: 20202701028@stu.ccucm.edu.cn., Tian J; Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: tina_yai@126.com., Tong X; Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: tongxiaolin@vip.163.com. |
| Source: | Ageing research reviews [Ageing Res Rev] 2026 Jan; Vol. 113, pp. 102938. Date of Electronic Publication: 2025 Nov 12. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: Elsevier Science Country of Publication: England NLM ID: 101128963 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9649 (Electronic) Linking ISSN: 15681637 NLM ISO Abbreviation: Ageing Res Rev Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford, UK : Elsevier Science, c2002- |
| MeSH Terms: | Diabetes Mellitus, Type 2*/metabolism , Diabetes Mellitus, Type 2*/therapy , Diabetes Mellitus, Type 2*/pathology , Insulin-Secreting Cells*/metabolism , Insulin-Secreting Cells*/pathology , Cellular Reprogramming*/physiology, Humans ; Animals ; Metabolic Reprogramming |
| Abstract: | Pancreatic beta cells are highly specialized cells that possess unique metabolic programs to ensure insulin secretion matches nutritional status for maintaining glucose homeostasis. However, in type 2 diabetes mellitus (T2DM), prolonged exposure to excessive nutrients (glucose, lipids) induces toxicity that leads to progressive beta cell failure and impaired insulin secretion, whose underlying mechanisms remain unclear. This review summarizes the distinctive metabolic features of pancreatic beta cells under physiological conditions and the mechanisms of glucolipotoxicity-driven metabolic reprogramming in pathological states (T2DM). Under chronic nutrient overload, beta cells undergo dynamic metabolic remodeling, resulting in the loss of characteristic metabolic programs and triggering interconnected stress damage networks including inflammation, oxidative stress, and endoplasmic reticulum stress. Meanwhile, disrupted transcriptional programs under metabolic stress also lead to the loss of beta cell identity. In response, beta cells attempt to evolve unique carbon flux metabolic reprogramming mechanisms to achieve fuel "detoxification." These processes are critical for identifying key nodes in beta cell metabolic reprogramming. Finally, the review outlines therapeutic strategies targeting beta cell metabolic reprogramming, particularly emerging approaches focusing on microRNAs and restoring beta cell identity and function. This article aims to delineate the key nodes in the transition of beta cells from physiological to pathological metabolic states, providing a theoretical basis for identifying reversible stages in disease progression and restoring metabolic flexibility to achieve beta cell functional protection. (Copyright © 2025 Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
| Contributed Indexing: | Keywords: Beta cells; Glycolipotoxicity; Metabolic flexibility; Metabolic reprogramming; Type 2 diabetes mellitus |
| Entry Date(s): | Date Created: 20251114 Date Completed: 20251202 Latest Revision: 20251202 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.arr.2025.102938 |
| PMID: | 41238064 |
| Database: | MEDLINE |
| ISSN: | 1872-9649 |
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| DOI: | 10.1016/j.arr.2025.102938 |