Electroacupuncture promotes the gastrointestinal motility of diabetic mice by CNP/NPR‐B‐cGMP and PDE3A‐cGMP signaling

Abstract

Background Electroacupuncture (EA) can promote gastrointestinal (GI) motility of diabetic mice, but the mechanism is not clearly elucidated. Natriuretic peptides (NPs) were related to the diabetes‐induced gut dysfunction of mice, which may be associated with ICC (interstitial cells of cajal). Besides, EA could increase the ICC of diabetic mice. Our aim was to explore whether EA can promote the gut motility by CNP/NPR‐B‐cGMP and PDE3A‐cGMP signaling in diabetic mice, and the relationship between NPs and ICC. Methods Wild C57BL/6 male mice were divided into five groups: control group, diabetic mellitus (DM group), diabetic mellitus plus sham EA group (SEA), diabetic mellitus plus low‐frequency EA group (LEA), and diabetic mellitus plus high‐frequency group (HEA). Gastrointestinal motility was assessed by gastric emptying and GI transit test. Immunofluorescence staining was applied to assess the expression level of CNP, NPR‐B, and c‐Kit. Western blot, PCR, and ELISA were used to detect the level of CNP, NPR‐B, PDE2A, PDE3A, c‐Kit, mSCF, and cGMP content. The correlativity between NPR‐B and mSCF was evaluated by Pearson's correlation and linear regression analyses. Key Results (a) EA could improve the GI dysfunction of diabetic mice. (b) CNP, NPR‐B, and cGMP contents were decreased, but the level of PDE3A, c‐Kit, and mSCF was increased in the EA groups. (c) There was a negative correlation between NPR‐B and mSCF among the groups. Conclusions and Inferences Electroacupuncture promotes the GI function by CNP/NPR‐B‐cGMP and PDE3A‐cGMP signaling in diabetic mice; up‐regulated mSCF/c‐Kit signaling by EA may be mediated partially via down‐regulation of CNP/NPR‐B signaling.

CD44 fucosylation on bone marrow-derived mesenchymal stem cells enhances homing and promotes enteric nervous system remodeling in diabetic mice

“…Consistent with previous studies, our results found that PGP9.5 and GFAP decreased in colon tissues of diabetic mice induced by STZ at 16 weeks. Diabetic colonic motility disorder is characterized by abdominal distension and constipation, and its pathophysiological characteristics include decreased colonic tension and contractility, slow peristalsis, and delayed emptying [ 7 , 31 – 33 ]. Moreover, in our study, we also found that compared with normal mice, the autonomic contractile ability of colonic muscles and the ability to respond to electric field stimulation in diabetic mice were reduced, the intestinal transmission ability was poor, and the fecal water content and frequency of defecation were reduced.…”

Electroacupuncture accelerates the delayed intestinal transit in POI by suppressing M1 like muscularis macrophages and IL6 secretion

“…It has been well established that the loss of ICCs contributed to the delayed GI motility 32,38 . Our previous and current study have proved both the high‐ and low‐frequency EA could restore impaired ICC in stomach and colon of diabetic rats and mice, resulting in the promotion of GI motility 1,4,5 . Unfortunately, to date, the mechanisms involved were not fully understood.…”

“…Electroacupuncture is the combination of the use of traditional Chinese acupuncture and an electrical current, which has been used to treat gastrointestinal disorders for many years. It has been reported that EA at ST‐36 improved the delayed gastric emptying and impaired accommodation in STZ‐induced diabetic rats 1,4,22 . Moreover, the delayed gastric emptying and gastric hypersensitivity were ameliorated by EA in the rodent model of functional dyspepsia 23 .…”

“…Electroacupuncture (EA) is a modification of traditional acupuncture that stimulated acupoints with electrical current instead of manual manipulations, appearing to be more reproducible in both clinical and research settings. During the last decades, a considerable number of clinical and basic research have proved the beneficial effect of EA on gastrointestinal (GI) motility disorders 1–5 . However, the mechanisms involved have not been understood completely.…”

Defective development and microcirculation of intestine in Npr2 mutant mice

“…Previous studies revealed that CNP/NPR-B and/or NPR-C signaling regulates contractility of the gastric antrum and large intestine 14 – 17 . It was also suggested that the CNP/NPR-B/cGMP signal may be related to ICC activity 18 – 20 , and vascular remodeling, and blood pressure 21 – 28 . Furthermore, CNP is also known to be related to adipocyte metabolism 29 , 30 .…”