PMID- 36740184
OWN - NLM
STAT- MEDLINE
DCOM- 20230424
LR  - 20230424
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 193
IP  - 5
DP  - 2023 May
TI  - TRPV1 Dysfunction Impairs Gastric Nitrergic Neuromuscular Relaxation in High-Fat 
      Diet-Induced Diabetic Gastroparesis Mice.
PG  - 548-557
LID - S0002-9440(23)00037-8 [pii]
LID - 10.1016/j.ajpath.2023.01.005 [doi]
AB  - Diabetic gastroparesis (DGP) is characterized by delayed gastric emptying of 
      solid food. Nitrergic neuron-mediated fundus relaxation and intragastric 
      peristalsis are pivotal for gastric emptying and are impaired in DGP. Transient 
      receptor potential vanilloid 1 (TRPV1) ion channels are expressed in 
      gastrointestinal vagal afferent nerves and have a potential role in relevant 
      gastrointestinal disorders. In this study, mice with high-fat diet (HFD)-induced 
      type 2 diabetes mellitus (T2DM), associated with gastroparesis, were used to 
      determine the role of TRPV1 in DGP. After feeding with HFD, mice exhibited 
      obesity, hyperglycemia, insulin resistance, and delayed gastric emptying. 
      Cholinergic- and nitrergic neuron-mediated neuromuscular contractions and 
      relaxation were impaired. The antral tone of the DGP mice was attenuated. 
      Interestingly, activating or suppressing TRPV1 facilitated or inhibited gastric 
      fundus relaxation in normal mice. These effects were neutralized by using a 
      nitric oxide synthase (NOS) inhibitor. Activation or suppression of TRPV1 also 
      increased or reduced NO release. TRPV1 was specifically localized with neuronal 
      NOS in the gastric fundus. These data suggest that TRPV1 activation facilitates 
      gastric fundus relaxation by regulating neuronal NOS and promoting NO release. 
      However, these effects and mechanisms disappeared in mice with DGP induced by HFD 
      diet. TRPV1 expression was only marginally decreased in the fundus of DGP mice. 
      TRPV1 dysfunction may be a potential mechanism underlying the dysfunction of DGP 
      gastric nitrergic neuromuscular relaxation.
CI  - Copyright (c) 2023 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Xu, Siyuan
AU  - Xu S
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou, China; Shenzhen Traditional Chinese Medicine Hospital, The Fourth 
      Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, 
      China.
FAU - Liang, Shaochan
AU  - Liang S
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Pei, Ying
AU  - Pei Y
AD  - School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Wang, Rui
AU  - Wang R
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Zhang, Yao
AU  - Zhang Y
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Xu, Yifei
AU  - Xu Y
AD  - Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical 
      College of Guangzhou University of Chinese Medicine, Shenzhen, China.
FAU - Huang, Bin
AU  - Huang B
AD  - Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical 
      College of Guangzhou University of Chinese Medicine, Shenzhen, China.
FAU - Li, Haiwen
AU  - Li H
AD  - Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical 
      College of Guangzhou University of Chinese Medicine, Shenzhen, China.
FAU - Li, Juanjuan
AU  - Li J
AD  - Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical 
      College of Guangzhou University of Chinese Medicine, Shenzhen, China.
FAU - Tan, Bo
AU  - Tan B
AD  - School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
FAU - Cao, Hongying
AU  - Cao H
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou, China. Electronic address: hycao@gzucm.edu.cn.
FAU - Guo, Shaoju
AU  - Guo S
AD  - Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical 
      College of Guangzhou University of Chinese Medicine, Shenzhen, China. Electronic 
      address: gsj1080@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230203
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (TRPV1 protein, mouse)
RN  - 0 (TRPV Cation Channels)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Gastroparesis/etiology/metabolism
MH  - *Diabetes Mellitus, Type 2/complications
MH  - Diet, High-Fat/adverse effects
MH  - Obesity/metabolism
MH  - Gastric Emptying
MH  - TRPV Cation Channels/metabolism
EDAT- 2023/02/06 06:00
MHDA- 2023/04/24 06:42
CRDT- 2023/02/05 19:28
PHST- 2022/10/12 00:00 [received]
PHST- 2022/12/30 00:00 [revised]
PHST- 2023/01/06 00:00 [accepted]
PHST- 2023/04/24 06:42 [medline]
PHST- 2023/02/06 06:00 [pubmed]
PHST- 2023/02/05 19:28 [entrez]
AID - S0002-9440(23)00037-8 [pii]
AID - 10.1016/j.ajpath.2023.01.005 [doi]
PST - ppublish
SO  - Am J Pathol. 2023 May;193(5):548-557. doi: 10.1016/j.ajpath.2023.01.005. Epub 
      2023 Feb 3.