Delayed gastric emptying in diabetic rats caused by decreased expression of cystathionine gamma lyase and H2S synthesis: in vitro and in vivo studies.
BACKGROUND
This study aimed to evaluate the role of H2S on gastric emptying rate (GER) and also to determine the effect of gastric distention on mRNA and protein expression of cystathionine β-lyase (CBS) and cystathionine γ-synthase (CSE) in diabetic-gastroparetic and normal rats.


METHODS
Adult normal rats intraperitoneally received either propargylglycine (PAG), L-cysteine or NaHS 30 min prior to GER marker (acetaminophen) to investigate H2S involvement in GER and the same protocols were performed in diabetes-induced gastroparesis rats. The role of calcitonin gene related peptide (CGRP) neurons in the prokinetic effect of endogenous H2S on GER was determined. The level of CBS and CSE expressions in response to gastric distention were also determined. The effect of H2S on frequency and tension of spontaneous contractions of gastric smooth muscle strips was investigated.


RESULTS
Our results showed that: (i) H2S and L-cysteine increased GER in gastroparetic and normal rats. (ii) The increased levels of CSE expression in response to gastric distention in diabetic rats were lower than in normal rats. (iii) PAG inhibited the excitatory effect of capsaicin on GER and on tension of spontaneous contractions of strips. (iv) Hydrogen sulphide increased the frequency and tension of spontaneous contractions of gastric strip muscles in normal and diabetic rats.


CONCLUSIONS
The results showed that delayed GER in diabetic rats can be due to down-regulation of H2S biosynthesis enzyme, CSE and suggested that a potential prokinetic role for H2S to treat the delayed gastric emptying in diabetic patients.
Physiology Research Center (PRC), Research Center for Infectious Diseases of Digestive System, Dept. of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. alimard77@gmail.com, mard-sa@ajums.ac.ir.
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Mard
Physiology Research Center (PRC), Research Center for Infectious Diseases of Digestive System, Dept. of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ahmadiiraj57@yahoo.com.
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Ahmadi
Physiology Research Center (PRC), Dept. of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Ahangarpour
Physiology Research Center (PRC), Dept. of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Gharib-Naseri
Physiology Research Center (PRC), Dept. of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Badavi
D000818:Animals; D003542:Cystathionine gamma-Lyase / Q000096:biosynthesis* / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005746:Gastric Emptying / Q000502:physiology*; D018589:Gastroparesis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar
D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
H2S; diabetic; gastric emptying rate; gastroparesis; rat