ArticleGastroenterology2008
Heme oxygenase-1 protects interstitial cells of Cajal from oxidative stress and reverses diabetic gastroparesis.
Article in Gastroenterology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 234 citations in OpenAlex.
- Electroacupuncture at ST-36 Protects Interstitial Cells of Cajal via Sustaining Heme Oxygenase-1 Positive M2 Macrophages in the Stomach of Diabetic Mice.Oxidative medicine and cellular longevity · 2018Trial
- Effects of hemin on heme oxygenase-1, gastric emptying, and symptoms in diabetic gastroparesis.Neurogastroenterology and motility · 2016Trial
- Effects of aspirin & simvastatin and aspirin, simvastatin, & lipoic acid on heme oxygenase-1 in healthy human subjects.Neurogastroenterology and motility · 2014Trial
- First-in-human study demonstrating pharmacological activation of heme oxygenase-1 in humans.Clinical pharmacology and therapeutics · 2010Trial
- Muscularis EGR1 Deficiency Impairs M2 Macrophage Polarization and Disrupts Gastric Motility in Diabetic Gastroparesis.Neurogastroenterology and motility · 2026Article
- Breath volatiles reflect diabetic gastroparesis and its recovery by activating NaExperimental & molecular medicine · 2026Article
- Changes in interstitial cells of Cajal calcium activity in a diabetic mouse model of delayed gastric emptying.The Journal of physiology · 2026Article
- Review
- Intestinal neuron-associated macrophages in health and disease.Nature immunology · 2025Review
- Impact of Gastroparesis on Outcomes After Pancreas Transplantation.Transplantation direct · 2025Article
- Current Concepts in Gastroparesis and Gastric Neuromuscular Disorders-Pathophysiology, Diagnosis, and Management.Diagnostics (Basel, Switzerland) · 2025Review
- Mass cytometric analysis of circulating monocyte subsets in a murine model of diabetic gastroparesis.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Unmasking Gastroparesis in Diabetes During Ramadan: Challenges and Management Strategies.Journal of clinical medicine · 2025Review
- Pharmacologic treatments for gastroparesis.Pharmacological reviews · 2025Review
- The impact of social determinants of health on diabetic gastroparesis: a retrospective analysis.Frontiers in public health · 2025Observational
- The critical role of muscularis macrophages in modulating the enteric nervous system function and gastrointestinal motility.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2024Review
- Oxidative Stress and Neural Dysfunction in Gastrointestinal Diseases: Can Stem Cells Offer a Solution?Stem cells translational medicine · 2023Article
- Hypoxia-Inducible Factor 1α Stabilization Restores Epigenetic Control of Nitric Oxide Synthase 1 Expression and Reverses Gastroparesis in Female Diabetic Mice.Gastroenterology · 2023Article
- New insights into muscularis macrophages in the gut: from their origin to therapeutic targeting.Immunologic research · 2023Review
- Adeno-associated virus-9 reverses delayed gastric emptying of solids in diabetic mice.Neurogastroenterology and motility · 2023Article
80 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsDiabetic gastroparesis (delayed gastric emptying) is a well-recognized complication of diabetes that causes considerable morbidity and makes glucose control difficult. Interstitial cells of Cajal, which express the receptor tyrosine kinase Kit, are required for normal gastric emptying. We proposed that Kit expression is lost during diabetic gastroparesis due to increased levels of oxidative stress caused by low levels of heme oxygenase-1 (HO-1), an important cytoprotective molecule against oxidative injury.
methodsGastric emptying was measured in nonobese diabetic mice and correlated with levels of HO-1 expression and activity. Endogenous HO-1 activity was increased by administration of hemin and inhibited by chromium mesoporphyrin.
resultsIn early stages of diabetes, HO-1 was up-regulated in gastric macrophages and remained up-regulated in all mice that were resistant to development of delayed gastric emptying. In contrast, HO-1 did not remain up-regulated in all the mice that developed delayed gastric emptying; expression of Kit and neuronal nitric oxide synthase decreased markedly in these mice. Loss of HO-1 up-regulation increased levels of reactive oxygen species. Induction of HO-1 by hemin decreased reactive oxygen species, rapidly restored Kit and neuronal nitric oxide synthase expression, and completely normalized gastric emptying in all mice. Inhibition of HO-1 activity in mice with normal gastric emptying caused a loss of Kit expression and development of diabetic gastroparesis.
conclusionsInduction of the HO-1 pathway prevents and reverses cellular changes that lead to development of gastrointestinal complications of diabetes. Reagents that induce this pathway might therefore be developed as therapeutics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.