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Liu Y, Xie J, Yu Z, Gong M, Li Q, Yang G, Xu B, Xu T. Electroacupuncture at ST25 mediated glial cells pruning of pancreatic TRPV1 neural synapse responds to neuropathy-associated beta cell dysfunction. Chin Med 2025; 20:65. [PMID: 40380290 DOI: 10.1186/s13020-025-01099-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 03/23/2025] [Indexed: 05/19/2025] Open
Abstract
Electroacupuncture (EA) is verified to modulate glycemic changes in T2DM, and this is partially related to sensory neurotransmitters. However, EA-mediated communication mechanism between them and acupoint specificity have not been fully clarified. Thus, we replicated the diabetic rat model induced by a high-fat diet/streptozotocin (HFD-STZ), and investigated the alleviating effects on insulin resistance (IR) and inflammation severity after EA at ST25. We also compared the effect difference of EA at ST37. Furthermore, we studied the changes of pancreatic sensory neurotransmitters and β cells (and their surrounding components) in detail. Serum glucose, insulin, IR, TNF-α and IL-10 were significantly elevated in model rats, and β cell function was impaired, which reversed by EA at ST25 or ST37 to varying degrees. EA at ST25 can enhance the expression of calcitonin gene-related peptide (CGRP), attenuate transient receptor potential vanilloid 1(TRPV1) and correct the secretion mismatch between them, while EA at ST37 has no such effect. Subsequently, EA at ST25-mediated TRPV1-CGRP-β cell circuit demonstrates an advantage in regulating glucose metabolism via direct insulin inhibition by CGRP. EA at ST25 rather than ST37 regulates the activity of peri-ilset glial cells and macrophages, playing a neuro-protective role and controlling inflammation. EA at ST37 exhibits its partial therapeutic effect on T2DM as it improves serum GLP-1. It also implies that the dominant target organ of ST37 may not be the pancreas, but other associated viscera. Hence, our study elucidates the EA-mediated glial cell via TRPV1-CGRP pathway regulation of β cell dysfunction after nerve lesion, and the hypoglycemic effect of ST25 is significantly better than that of ST37.
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Affiliation(s)
- Yun Liu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiahui Xie
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhi Yu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China
| | - Meirong Gong
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China
| | - Qian Li
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China
| | - Guanhu Yang
- Research Department, Swiss University of Traditional Chinese Medicine, Bad Zurzach, Switzerland
- Department of Specialty Medicine, Ohio University, Athens, 43055, USA
| | - Bin Xu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China.
| | - Tiancheng Xu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China.
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Liu Y, Yu Z, Wang X, Yuan MQ, Lu MJ, Gong MR, Li Q, Xia YB, Yang GH, Xu B, Litscher G, Xu TC. Neurophysiological mechanisms of electroacupuncture in regulating pancreatic function and adipose tissue expansion. World J Diabetes 2025; 16. [DOI: doi：10.4239/wjd.v16.i5.101354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND
Electroacupuncture (EA) has been recognized for its beneficial effects on glucolipid metabolism, potentially through the regulation of sensory nerve coordination. The expandability of peripancreatic adipose tissue (PAT) is implicated in the transition from obesity to type 2 diabetes mellitus (T2DM). However, the specific pancreatic responses to EA require further elucidation.
AIM
To investigate the influence of EA on pancreatic glucolipid reduction level in a high-fat diet (HFD) rat model.
METHODS
To delineate the precise pathway through which EA mediates interactions between PAT and islets, we assessed the expression levels of NGF, TRPV1, insulin, as well as other proteins in the pancreas and PAT. This approach enabled us to identify the acupoints that are most conducive to optimizing glycolipid metabolism.
RESULTS
The ST25, LI11 and ST37 groups attenuated HFD-induced obesity and insulin resistance (IR) to distinct degrees, with ST25 group having the greatest effect. EA at ST25 was found to modify the local regulatory influence of PAT on the pancreatic intrinsic nervous system. Specifically, EA at ST25 obviously activated the TRPV1-CGRP-islet beta cell pathway, contributing to the relief of glucolipid metabolic stress. The beneficial effects were abrogated following the chemical silencing of TRPV1 sensory afferents, confirming their indispensable role in EA-mediated regulation of islet and PAT function. Furthermore, in TRPV1 knockout mice, a reduction in PAT inflammation was observed, along with the recovery of islet beta cell function. EA at LI11 and ST37 demonstrated anti-inflammatory properties and helped ameliorate IR.
CONCLUSION
The PAT ecological niche influenced the progression from obesity to T2DM through various immunometabolic pathways. EA at ST25 could regulate glucolipid metabolism via the TRPV1-CGRP-islet beta cell pathway.
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Liu Y, Yu Z, Wang X, Yuan MQ, Lu MJ, Gong MR, Li Q, Xia YB, Yang GH, Xu B, Litscher G, Xu TC. Neurophysiological mechanisms of electroacupuncture in regulating pancreatic function and adipose tissue expansion. World J Diabetes 2025; 16:101354. [DOI: 10.4239/wjd.v16.i5.101354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 02/12/2025] [Accepted: 03/14/2025] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND Electroacupuncture (EA) has been recognized for its beneficial effects on glucolipid metabolism, potentially through the regulation of sensory nerve coordination. The expandability of peripancreatic adipose tissue (PAT) is implicated in the transition from obesity to type 2 diabetes mellitus (T2DM). However, the specific pancreatic responses to EA require further elucidation.
AIM To investigate the influence of EA on pancreatic glucolipid reduction level in a high-fat diet (HFD) rat model.
METHODS To delineate the precise pathway through which EA mediates interactions between PAT and islets, we assessed the expression levels of NGF, TRPV1, insulin, as well as other proteins in the pancreas and PAT. This approach enabled us to identify the acupoints that are most conducive to optimizing glycolipid metabolism.
RESULTS The ST25, LI11 and ST37 groups attenuated HFD-induced obesity and insulin resistance (IR) to distinct degrees, with ST25 group having the greatest effect. EA at ST25 was found to modify the local regulatory influence of PAT on the pancreatic intrinsic nervous system. Specifically, EA at ST25 obviously activated the TRPV1-CGRP-islet beta cell pathway, contributing to the relief of glucolipid metabolic stress. The beneficial effects were abrogated following the chemical silencing of TRPV1 sensory afferents, confirming their indispensable role in EA-mediated regulation of islet and PAT function. Furthermore, in TRPV1 knockout mice, a reduction in PAT inflammation was observed, along with the recovery of islet beta cell function. EA at LI11 and ST37 demonstrated anti-inflammatory properties and helped ameliorate IR.
CONCLUSION The PAT ecological niche influenced the progression from obesity to T2DM through various immunometabolic pathways. EA at ST25 could regulate glucolipid metabolism via the TRPV1-CGRP-islet beta cell pathway.
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Affiliation(s)
- Yun Liu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Zhi Yu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Xuan Wang
- College of Traditional Chinese Medicine, Jiangsu Vocational College of Medicine, Yancheng 224000, Jiangsu Province, China
| | - Ming-Qian Yuan
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Meng-Jiang Lu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Mei-Rong Gong
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Qian Li
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - You-Bing Xia
- Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
| | - Guan-Hu Yang
- Department of Specialty Medicine, Ohio University, Athens, OH 45701, United States
| | - Bin Xu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Gerhard Litscher
- High-Tech Acupuncture and Digital Chinese Medicine, Swiss University of Traditional Chinese Medicine, Bad Zurzach 5530, Switzerland
| | - Tian-Cheng Xu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
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