2. Academic Validation
  3. Didymin protects pancreatic beta cells by enhancing mitochondrial function in high-fat diet-induced impaired glucose tolerance

Didymin protects pancreatic beta cells by enhancing mitochondrial function in high-fat diet-induced impaired glucose tolerance

  • Diabetol Metab Syndr. 2024 Jan 3;16(1):7. doi: 10.1186/s13098-023-01244-1.
Jingwen Yang 1,  Ying Zou 1,  Xiaoyu Lv 1,  Jun Chen 1,  Chen Cui 2,  Jia Song 1,  Mengmeng Yang 1,  Huiqing Hu 1,  Jing Gao 1,  Longqing Xia 1,  Liming Wang 1,  Li Chen 1 3 4 5 6 7,  Xinguo Hou 8 9 10 11 12 13
Affiliations

Affiliations

  • 1 Department of Endocrinology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, 250012, Jinan, Shandong, China.
  • 2 Department of Endocrinology, The Second Hospital of Shandong University, Jinan, China.
  • 3 Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China.
  • 4 Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, China.
  • 5 Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China.
  • 6 National Key Laboratory for Innovation and Transformation of Luobing Theory, Jinan, China.
  • 7 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Jinan, China.
  • 8 Department of Endocrinology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, 250012, Jinan, Shandong, China. [email protected].
  • 9 Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China. [email protected].
  • 10 Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, China. [email protected].
  • 11 Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China. [email protected].
  • 12 National Key Laboratory for Innovation and Transformation of Luobing Theory, Jinan, China. [email protected].
  • 13 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Jinan, China. [email protected].
PMID: 38172956 DOI: 10.1186/s13098-023-01244-1
Abstract

Purpose: Prolonged exposure to plasma free fatty acids (FFAs) leads to impaired glucose tolerance (IGT) which can progress to type 2 diabetes (T2D) in the absence of timely and effective interventions. High-fat diet (HFD) leads to chronic inflammation and oxidative stress, impairing pancreatic beta cell (PBC) function. While Didymin, a flavonoid glycoside derived from citrus fruits, has beneficial effects on inflammation dysfunction, its specific role in HFD-induced IGT remains yet to be elucidated. Hence, this study aims to investigate the protective effects of Didymin on PBCs.

Methods: HFD-induced IGT mice and INS-1 cells were used to explore the effect and mechanism of Didymin in alleviating IGT. Serum glucose and Insulin levels were measured during the glucose tolerance and Insulin tolerance tests to evaluate PBC function and Insulin resistance. Next, RNA-seq analysis was performed to identify the pathways potentially influenced by Didymin in PBCs. Furthermore, we validated the effects of Didymin both in vitro and in vivo. Mitochondrial electron transport inhibitor (Rotenone) was used to further confirm that Didymin exerts its ameliorative effect by enhancing mitochondria function.

Results: Didymin reduces postprandial glycemia and enhances 30-minute postprandial Insulin levels in IGT mice. Moreover, Didymin was found to enhance mitochondria biogenesis and function, regulate Insulin secretion, and alleviate inflammation and Apoptosis. However, these effects were abrogated with the treatment of Rotenone, indicating that Didymin exerts its ameliorative effect by enhancing mitochondria function.

Conclusions: Didymin exhibits therapeutic potential in the treatment of HFD-induced IGT. This beneficial effect is attributed to the amelioration of PBC dysfunction through improved mitochondrial function.

Keywords

Didymin; High-fat diet; Impaired glucose tolerance; Mitochondrial function; Pancreatic beta cell.

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