Delayed gastric emptying in diabetic rats caused by decreased expression of cystathionine gamma lyase and H sub(2)S synthesis: in vitro and in vivo studies

• Published in: Neurogastroenterology and motility 2016-11, Vol.28 (11), p.1677-1689
• Main Authors: Mard, SA, Ahmadi, I, Ahangarpour, A, Gharib-Naseri, M K, Badavi, M
• Format: Article
• Language: English
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.12867

Background This study aimed to evaluate the role of H sub(2)S on gastric emptying rate (GER) and also to determine the effect of gastric distention on mRNA and protein expression of cystathionine beta -lyase (CBS) and cystathionine gamma -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 H sub(2)S 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 H sub(2)S on GER was determined. The level of CBS and CSE expressions in response to gastric distention were also determined. The effect of H sub(2)S on frequency and tension of spontaneous contractions of gastric smooth muscle strips was investigated. Key Results Our results showed that: (i) H sub(2)S 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 & Inferences The results showed that delayed GER in diabetic rats can be due to down-regulation of H sub(2)S biosynthesis enzyme, CSE and suggested that a potential prokinetic role for H sub(2)S to treat the delayed gastric emptying in diabetic patients. The results of the present study showed that endogenous and exogenous H sub(2)S and L-cysteine accelerate the GER in normal and diabetic rats. The molecular findings were also showed that mRNA and protein expression of cystathionine gamma lyase, the main responsible enzyme for H sub(2)S synthesis in the rat stomach decreased in diabetic rats.