Delayed gastric emptying in diabetic rats caused by decreased expression of cystathionine gamma lyase and H2S synthesis: in vitro and in vivo studies

Mard, Seyyed Ali; Ahmadi, Iraj; Ahangarpour, Akram; Gharib-Naseri, Mohammad Kazem; Badavi, Mohammad

doi:10.1111/nmo.12867

Cited by 13 publications

(16 citation statements)

References 30 publications

(87 reference statements)

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“…Analysis of qRT‐PCR results showed that mRNA expressions of CSE, and CBS in smooth muscles of jejunum, ileum, and colon in diabetic rats decreased compared to normal rats. In agreement, the authors recently have shown that the mRNA expression of CSE decreased in gastric mucosa, and muscles in alloxan‐induced diabetic rats . In a previous study, Yamane et al.…”

Section: Discussionsupporting

confidence: 70%

“…NaHS at dose of 0.32 mg/kg not only decreased but also non‐significantly increased the total number, and water content of FP in normal rats. This effect could partly be due to its prokinetic effect as shown by authors in a previous study . Moreover, it has been shown that the effect of NaHS on intestinal motility was dependent on the dose of NaHS.…”

Section: Discussionmentioning

confidence: 58%

“…The present results also showed that L‐cysteine at 100 mg/kg not only decreased but also increased the total number of FP in normal rats. This effect could largely be secondary to its prokinetic effect as shown by authors in a previous study …”

Section: Discussionmentioning

confidence: 73%

“…In vitro studies have been shown that H 2 S decrease the frequency and tension of spontaneous contractions of the smooth muscles of gastric fundus, jejunum and colon in rat, mouse and human . A recent report by authors showed that H 2 S is involved in the pathophysiology of diabetic gastroparesis …”

Section: Introductionmentioning

confidence: 99%

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Antidiarrheal effect of sodium hydrosulfide in diabetic rats: In vitro and in vivo studies

Saghazadeh‐Dezfuli

Fanaei

Gharib-Naseri

et al. 2017

Neurogastroenterology Motil

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antidiarrheal effect of sodium hydrosulfide in diabetic rats: In vitro and in vivo studies

Saghazadeh‐Dezfuli

Fanaei

Gharib-Naseri

et al. 2017

Neurogastroenterology Motil

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“…In this condition, it was also found that lack of well-coordinated gastric contractions between fundic and pyloric regions impairing gastric emptying at advanced stages (Ariga et al 2008). Both delayed gastric emptying (Miyamoto et al 2001;Camilleri et al 2010;Mard et al 2016) and accelerated emptying (Phillips et al 1992;Young et al 1995;Green et al 1997) have been noticed during diabetes.…”

Section: Discussionmentioning

confidence: 99%

Mild diabetes: long‐term effects on gastric motility evaluated in rats

Hauschildt

Corá

Volpato

et al. 2018

Int J Experimental Path

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Moderate hyperglycaemic levels seem to be related to abnormal gastric motility in diabetes mellitus. However, experimental models designed to evaluate the relationship between motility and diabetes over time are not yet well established. Our objective was to investigate the long-term effects of mild diabetes on gastric motility in rats. Newborn male rats received streptozotocin (mild diabetes groups - MD) or vehicle (control groups - C), and both groups were evaluated after 3 (C3 and MD3) and 6 months (C6 and MD6) postinduction. Mild diabetic animals (MD3 and MD6) showed moderately elevated blood glucose and decreased insulin levels compared with control (C3 and C6). Insulin secretion was enhanced in MD6 compared with MD3, most likely due to partial β-cell regeneration indicated by HOMA-β. In HOMA-IR, it was noticed that MD6 animals had impaired insulin response compared with MD3. Gastric emptying was faster, amplitude of contraction was stronger in MD6 compared with MD3, and in both groups, the differences were significant when compared with control animals. A significant abnormal rhythmic index was calculated for the mild diabetic groups, despite unchanged mean frequency of contraction. In conclusion, despite increased insulin levels over time, constant levels of moderate hyperglycaemia are also related to abnormal gastric motility and impairment of gastric function.

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Exogenous H₂S promotes ubiquitin‐mediated degradation of SREBP1 to alleviate diabetic cardiomyopathy via SYVN1 S‐sulfhydration

Zhang,

Wang,

et al. 2023

J cachexia sarcopenia muscle

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BackgroundDiabetic cardiomyopathy, a distinctive complication of diabetes mellitus, has been correlated with the presence of intracellular lipid deposits. However, the intricate molecular mechanisms governing the aberrant accumulation of lipid droplets within cardiomyocytes remain to be comprehensively elucidated.MethodsBoth obese diabetic (db/db) mice and HL‐1 cells treated with 200 μmol/L palmitate and 200 μmol/L oleate were used to simulate type 2 diabetes conditions. Transmission electron microscopy is employed to assess the size and quantity of lipid droplets in the mouse hearts. Transcriptomics analysis was utilized to interrogate mRNA levels. Lipidomics and ubiquitinomics were employed to explore the lipid composition alterations and proteins participating in ubiquitin‐mediated degradation in mice. Clinical data were collected from patients with diabetes‐associated cardiomyopathy and healthy controls. Western blot analysis was conducted to assess the levels of proteins linked to lipid metabolism, and the biotin‐switch assay was employed to quantify protein cysteine S‐sulfhydration levels.ResultsThe administration of H2S donor, NaHS, effectively restored hydrogen sulfide levels in both the cardiac tissue and plasma of db/db mice (+7%, P < 0.001; +5%, P < 0.001). Both db/db mice (+210%, P < 0.001) and diabetic patients (+83%, P = 0.22, n = 5) exhibit elevated plasma triglyceride levels. Treatment with GYY4137 effectively lowers triglyceride levels in db/db mice (−43%, P = 0.007). The expression of cystathionine gamma‐lyase and HMG‐CoA reductase degradation protein 1 (SYVN1) was decreased in db/db mice compared with the wild‐type mice (cystathionine gamma‐lyase: −31%, P = 0.0240; SYVN1: −35%, P = 0.01), and NaHS‐treated mice (SYVN1: −31%, P = 0.03). Conversely, the expression of sterol regulatory element‐binding protein 1 (SREBP1) was elevated (+91%, P = 0.007; +51%, P = 0.03 compared with control and NaHS‐treated mice, respectively), along with diacylglycerol O‐acyltransferase 1 (DGAT1) (+95%, P = 0.001; +35%, P = 0.02) and 1‐acylglycerol‐3‐phosphate O‐acyltransferase 3 (AGPAT3) (+88%, P = 0.01; +22%, P = 0.32). Exogenous H2S led to a reduction in lipid droplet formation (−48%, P < 0.001), restoration of SYVN1 expression, modification of SYVN1's S‐sulfhydration status and enhancement of SREBP1 ubiquitination. Overexpression of SYVN1 mutated at Cys115 decreased SREBP1 ubiquitination and increased the number of lipid droplets.ConclusionsExogenous H2S enhances ubiquitin‐proteasome degradation of SREBP1 and reduces its nuclear translocation by modulating SYVN1's cysteine S‐sulfhydration. This pathway limits lipid droplet buildup in cardiac myocytes, ameliorating diabetic cardiomyopathy.

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Delayed gastric emptying in diabetic rats caused by decreased expression of cystathionine gamma lyase and H₂S synthesis: in vitro and in vivo studies

Abstract: The results showed that delayed GER in diabetic rats can be due to down-regulation of H S biosynthesis enzyme, CSE and suggested that a potential prokinetic role for H S to treat the delayed gastric emptying in diabetic patients.

Cited by 13 publications

References 30 publications

Antidiarrheal effect of sodium hydrosulfide in diabetic rats: In vitro and in vivo studies

Antidiarrheal effect of sodium hydrosulfide in diabetic rats: In vitro and in vivo studies

Mild diabetes: long‐term effects on gastric motility evaluated in rats

Exogenous H₂S promotes ubiquitin‐mediated degradation of SREBP1 to alleviate diabetic cardiomyopathy via SYVN1 S‐sulfhydration

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Delayed gastric emptying in diabetic rats caused by decreased expression of cystathionine gamma lyase and H2S synthesis: in vitro and in vivo studies

Abstract: The results showed that delayed GER in diabetic rats can be due to down-regulation of H S biosynthesis enzyme, CSE and suggested that a potential prokinetic role for H S to treat the delayed gastric emptying in diabetic patients.

Cited by 13 publications

References 30 publications

Antidiarrheal effect of sodium hydrosulfide in diabetic rats: In vitro and in vivo studies

Antidiarrheal effect of sodium hydrosulfide in diabetic rats: In vitro and in vivo studies

Mild diabetes: long‐term effects on gastric motility evaluated in rats

Exogenous H2S promotes ubiquitin‐mediated degradation of SREBP1 to alleviate diabetic cardiomyopathy via SYVN1 S‐sulfhydration

Contact Info

Product

Resources

About

Delayed gastric emptying in diabetic rats caused by decreased expression of cystathionine gamma lyase and H₂S synthesis: in vitro and in vivo studies

Exogenous H₂S promotes ubiquitin‐mediated degradation of SREBP1 to alleviate diabetic cardiomyopathy via SYVN1 S‐sulfhydration