Inhibiting Fatty Acid Amide Hydrolase Ameliorates Enteropathy in Diabetic Mice: A Cannabinoid 1 Receptor Mediated Mechanism
1
Center of Emphasis in Diabetes and Metabolism, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA
2
Division of Gastroenterology, Department of Internal Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA
3
Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA
*
Author to whom correspondence should be addressed.
Vet. Sci. 2022, 9(7), 364; https://doi.org/10.3390/vetsci9070364
Submission received: 7 April 2022
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Revised: 9 July 2022
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Accepted: 13 July 2022
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Published: 16 July 2022
(This article belongs to the Special Issue Exploring Animal Models for Diabetes Research)
Simple Summary
Gastrointestinal (GI) disorder is a debilitating complication of diabetes that interferes with the quality of life of the patients and current medical treatments are not very effective. High blood glucose levels in diabetics and the duration of diabetes could lead to complications of the GI tract, such as enteropathy and gastroparesis. Enteropathy is a disorder of the GI tract and can manifest as diarrhea, abdominal pain, constipation, and fecal incontinence. About 20% of patients affected with long-standing diabetes are at risk of diarrhea or fecal incontinence. This study was focused on assessing specific GI symptoms as well as manifestations in Type 1 diabetic mice and evaluated the treatment options for this distressing condition.
Abstract
Gastrointestinal (GI) dysmotility in diabetics exhibits fecal incontinence or constipation which affects patients’ quality of life. In this study, we aimed to understand the pattern of GI transit in type 1 diabetic (T1D) mice and whether inhibiting endocannabinoid degradation would exhibit therapeutic effect. Whole gut-transit time and fecal-pellet output were measured at 16 week post-diabetes. T1D mice treated with fatty acid amide hydrolase (FAAH) inhibitor URB597 showed reduced fecal output as well as improved gut transit time. Cannabinoid 1 receptor antagonist, AM251 blocked the effects of URB597, which may demonstrate that FAAH inhibitor is a potential remedial strategy for GI dysmotility.
