OBJECTIVE: Diabetes-induced gastrointestinal (GI) motility disorders are increasingly prevalent. Damage to the enteric nervous system (ENS), composed primarily of enteric neurons and glial cells, is an essential mechanism involved in these disorders. Although electroacupuncture (EA) has shown the potential to mitigate enteric neuronal loss, its mechanism is not fully understood. Additionally, the effects of EA on enteric glial cells have not been investigated. Enteric neural precursor cells (ENPCs) contribute to the structural and functional integrity of the ENS, yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored. This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved. METHODS: Transgenic mice were used to trace Nestin⁺/nerve growth factor receptor (Ngfr)⁺ ENPCs labeled with green fluorescent protein (GFP) in vivo. Mice were randomly divided into four groups: control, diabetes mellitus (DM), DM + sham EA, and DM + EA. The effects of EA on diabetic mice were evaluated by GI motility, ENS structure, and ENPC differentiation. Glial cell line-derived neurotrophic factor (GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms. RESULTS: EA alleviated diabetes-induced GI motility disorders, as indicated by reduced whole gut transit time, shortened colonic bead expulsion time, and enhanced smooth muscle contractility. Furthermore, EA attenuated diabetes-induced losses of enteric neurons and glial cells, thereby restoring ENS integrity. Notably, EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons. However, immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein⁺ glial cells and GFP-labeled ENPCs. Mechanistically, GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice. CONCLUSION EA facilitates ENS repair by promoting Nestin⁺/Ngfr⁺ ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling, and driving enteric gliogenesis from non-Nestin⁺/Ngfr⁺ ENPCs. These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration. Please cite this article as: Guo JL, Liu S, Ding SJ, Yang X, Du F. Electroacupuncture at ST36 improves gastrointestinal motility disorders by promoting enteric nervous system regeneration through GDNF/Ret signaling in diabetic mice. J Integr Med. 2025; 23(5):548-559.
Animals ; Electroacupuncture ; Enteric Nervous System/physiology* ; Gastrointestinal Motility/physiology* ; Glial Cell Line-Derived Neurotrophic Factor/metabolism* ; Diabetes Mellitus, Experimental/therapy* ; Signal Transduction ; Mice ; Gastrointestinal Diseases/physiopathology* ; Proto-Oncogene Proteins c-ret/metabolism* ; Mice, Transgenic ; Male ; Nerve Regeneration ; Neural Stem Cells ; Mice, Inbred C57BL ; Acupuncture Points

Live imaging has become an essential tool to investigate the coordinated activity and output of cellular networks. Within the last decade, 2 Nobel prizes have been awarded to recognize innovations in the field of imaging: one for the discovery, use, and optimization of the green fluorescent protein (2008) and the second for the development of super-resolved fluorescence microscopy (2014). New advances in both optogenetics and microscopy now enable researchers to record and manipulate activity from specific populations of cells with better contrast and resolution, at higher speeds, and deeper into live tissues. In this review, we will discuss some of the recent developments in microscope technology and in the synthesis of fluorescent probes, both synthetic and genetically encoded. We focus on how live imaging of cellular physiology has progressed our understanding of the control of gastrointestinal motility, and we discuss the hurdles to overcome in order to apply the novel tools in the field of neurogastroenterology and motility.
Awards and Prizes ; Enteric Nervous System ; Fluorescence ; Fluorescent Dyes ; Gastrointestinal Motility ; Microscopy ; Microscopy, Fluorescence ; Optogenetics ; Physiology

Slow transit constipation(STC)is the common type of chronic idiopathic constipation. Due to failure of routine conservative treatment, laxatives abuse is the most choice for majority of the patients, which could damage the enteric nervous system and result in aggravation of constipation. Resection of the slow transit colon is the ultimate option for some patients. It is hard to prevent and treat STC clinically because of the unknown pathophysiologic mechanism. Abnormalities of enteric neurotransmitters such as VIP, SP, NOS and decreased number of interstitial cells of Cajal have been described in the colon of the patients with STC. However, long term application of stimulant laxatives can also result in the almost same changes in the colon. Exploration of the potential relationship among the above reported abnormalities is the direction of future study.
Constipation ; physiopathology ; Enteric Nervous System ; physiopathology ; Gastrointestinal Transit ; physiology ; Humans ; Interstitial Cells of Cajal ; cytology

Successful assessing intestinal lumen content with ultrasound signals might lay a strong basis for the development of the artificial anal sphincter. In the present study, we utilized a modified MLU02-212 ultrasonic gas bubble detector to test the distal part of proximal colon in each rabbit, for the group of twenty healthy New Zealand rabbits. Voltage signals of solid, liquid, gas and empty content of the lumen were collected and compared. The results indicated that there were significant differences among the voltage signals in the 4 conditions (P = 0.000), respectively. Multiple comparison showed significant differences existed in any pair of the four conditions (P = 0.000). Three signal non-overlapping regions existed in these 4 conditions. Thus it seemed that ultrasound could be utilized to distinguish various contents inside the intestinal lumen and could act as "artificial sensory nerve".
Anal Canal ; innervation ; physiology ; Animals ; Artificial Organs ; Colon ; diagnostic imaging ; Enteric Nervous System ; physiology ; Fecal Incontinence ; surgery ; Female ; Gastrointestinal Contents ; Gastrointestinal Motility ; physiology ; Male ; Rabbits ; Sensory Receptor Cells ; physiology ; Ultrasonography

Interstitial cells of Cajal (ICCs) are located in most parts of the digestive system. Although they have been found over 100 years, their functions began to be unravelled only recently. ICCs are considered as pacemaker cells which elicit spontaneous rhythmic electric activity termed "basic electrical rhythm" or "slow waves" in gastrointestinal tract. Moreover, they also mediate neurotransmission from neurons to smooth muscle in gastrointestinal tract. ICC-like cells also exist in other visceral smooth muscles, such as urinary tract, genital system and vascular smooth muscle. In this paper we review the progress of research about the functions of visceral ICCs.
Animals ; Biological Clocks ; physiology ; Enteric Nervous System ; physiology ; Gastrointestinal Motility ; physiology ; Gastrointestinal Tract ; physiology ; Humans ; Interstitial Cells of Cajal ; physiology ; Myocytes, Smooth Muscle ; physiology ; Periodicity ; Synaptic Transmission ; physiology ; Viscera ; physiology

Animals ; Enteric Nervous System ; cytology ; Gastrointestinal Diseases ; etiology ; Gastrointestinal Motility ; physiology ; Humans ; Intestinal Mucosa ; cytology ; Intestines ; cytology ; innervation ; Muscle, Smooth ; cytology ; physiology ; Myenteric Plexus ; cytology ; Proto-Oncogene Proteins c-kit ; analysis