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The role of endoplasmic reticulum stress in gut-pancreas axis dysfunction in type 2 diabetes
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Li-ran LEI1, 2, Ya-xin FU1, 2, Quan LIU1, 2, 3, Jia-yu ZHAI1, 2, Zhu-fang SHEN1, 2, 3, Hui CAO1, 2, 3, *, Shuai-nan LIU1, 2, 3, *
Acta Pharmaceutica Sinica | 2024, 59(12) : 3189 - 3198
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Acta Pharmaceutica Sinica | 2024, 59(12): 3189-3198
The role of endoplasmic reticulum stress in gut-pancreas axis dysfunction in type 2 diabetes
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Li-ran LEI1, 2, Ya-xin FU1, 2, Quan LIU1, 2, 3, Jia-yu ZHAI1, 2, Zhu-fang SHEN1, 2, 3, Hui CAO1, 2, 3, *, Shuai-nan LIU1, 2, 3, *
Affiliations
  • 1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • 2. Diabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • 3. Beijing Key Laboratory of Polymorphic Drugs, Beijing 100050, China
Published: 2024-12-12 doi: 10.16438/j.0513-4870.2024-0799
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Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by chronic hyperglycemia, hyperlipidemia, and peripheral insulin resistance. Endoplasmic reticulum stress (ERS), a response to cellular stress, is activated across various tissues during the progression of T2DM, leading to disruptions in protein synthesis. Notably, epithelial and endocrine cells with hormone-secreting functions are particularly vulnerable to functional impairments induced by ERS. The gut-pancreas axis is essential for regulating metabolism and the progression of T2DM. Intestinal epithelial L cells, integral to the intestinal barrier, can secrete the glucagon-like peptide-1 (GLP-1). This hormone promotes insulin secretion from pancreatic β-cells and plays a critical role in glucose metabolism. Importantly, ERS plays a critical role in regulating glucolipid-induced dysfunction of gut-pancreas axis. For instance, ERS is involved in regulating the intestinal barrier and the secretion of GLP-1 as well as insulin. Therefore, ERS can be a potential target for T2DM treatment. In this paper, we review the regulatory roles of ERS in the gut-pancreas axis during the development of T2DM, and summarize the therapeutic drugs and strategies targeting ERS for T2DM treatment.

endoplasmic reticulum stress  /  gut-pancreas axis  /  intestinal barrier  /  glucagon-like peptide-1  /  β-cell  /  type 2 diabetes
Li-ran LEI, Ya-xin FU, Quan LIU, Jia-yu ZHAI, Zhu-fang SHEN, Hui CAO, Shuai-nan LIU. The role of endoplasmic reticulum stress in gut-pancreas axis dysfunction in type 2 diabetes[J]. Acta Pharmaceutica Sinica, 2024 , 59 (12) : 3189 -3198 . DOI: 10.16438/j.0513-4870.2024-0799
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Year 2024 volume 59 Issue 12
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doi: 10.16438/j.0513-4870.2024-0799
  • Receive Date：2024-08-19
  • Online Date：2025-11-24
  • Published：2024-12-12
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History
  • Received：2024-08-19
  • Revised：2024-09-29
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Affiliations
    1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
    2. Diabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
    3. Beijing Key Laboratory of Polymorphic Drugs, Beijing 100050, China
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小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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