Colonic motor dysfunction in human diabetes is associated with enteric neuronal loss and increased oxidative stress (original) (raw)
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Alterations of colonic contractility in long-term diabetic rat model
Journal of …, 2011
Methods The characteristics of colonic smooth muscle were investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. These results were compared to those obtained from Long-Evans Tokushima Otsuka (LETO) control rats ...
Clinical and experimental gastroenterology, 2017
Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. We aimed to characterize the stimulus-response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK) type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes. Seven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress-strain, spike rate increase ratio (SRIR), and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discha...
Journal of Neuroscience Research, 1989
Peripheral neuropathy is a correlate of experimental diabetes induced in rats by means of a single injection of alloxan. The autonomic and enteric innervation of the gut are profoundly affected in the small intestine of such animals. A complex process of denervation and hyperinnervation of the gut wall of diabetic animals is observed. It was previously reported that the cholinergic parasympathetic innervation of the intestine is markedly reduced. We have found that noradrenergic sympathetic axons hyperinnervate the duodenum of diabetic rats, whereas noradrenaline levels are significantly reduced in the jejunum. The putative enteric neurotransmitter dopamine is also present in higher levels in the duodenum. The intrinsic peptidergic neurons of the gut are deeply affected as well in diabetic rats. Substance P and met-enkephalin content are remarkably reduced throughout the small intestine, whereas vasoactive intestinal polypeptide levels (VIP) are significantly increased in the duodenum. Indeed, immunocytochemical staining of the ileum did reveal hypertrophy of VIP-positive axons in diabetic rats. The intrinsic serotoninergic innervation of the gut is apparently unaffected. Our results indicate that the changes of gut innervation observed in experimental diabetes are consistent with increased content and also likely with hyperinnervation by the neuronal systems involved in smooth muscle relaxation and decreased content and with denervation by those systems with smooth muscle contraction properties. Such a perturbed gut innervation may be responsible of the gastrointestinal dysfunctions that are among the most common complications of diabetes.
Autonomic Neuroscience, 2001
Changes in enteric neurons containing various neurotransmitters in the colon have been described in diabetic rats; however, how these Ž . changes are related to colonic motility disorders remains unclear. Nitric oxide NO is known to be an important inhibitory neurotransmitter in the enteric nervous system. In the present study, we investigated the peristaltic reflex using our modified Trendelenburg's method to evaluate the differences in enteric nitrergic neurons of the distal colon between spontaneously diabetic rats and their sibling control rats. We measured maximum intraluminal pressure, threshold pressure and propagation distance of the reflex contraction. These diabetic rats showed a greater maximum intraluminal pressure than that in the control rats. N G -nitro-L-arginine methyl Ž . ester L-NAME significantly increased the maximum pressure in the control rats. Although L-arginine did not change the maximum Ž . pressure, sodium nitroprusside SNP significantly decreased it in these diabetic rats. Nicotinamide adenine dinucleotide phosphate Ž . NADPH diaphorase reactivities in the myenteric plexus were much weaker in the diabetic rats than those in the control rats. These results indicate that the colonic peristaltic reflex is enhanced by impairment of enteric nitrergic inhibitory neurons in spontaneously diabetic rats. q
Diabetes-induced mechanophysiological changes in the small intestine and colon
World Journal of Diabetes
, is a peer-reviewed open access academic journal that aims to guide clinical practice and improve diagnostic and therapeutic skills of clinicians. WJD covers topics concerning α, β, δ and PP cells of the pancreatic islet, the effect of insulin and insulinresistance, pancreatic islet transplantation, adipose cells and obesity. We encourage authors to submit their manuscripts to WJD. We will give priority to manuscripts that are supported by major national and international foundations and those that are of great clinical significance.
Exogenous glucagon-like peptide 1 reduces contractions in human colon circular muscle
Journal of Endocrinology, 2014
Glucagon-like peptide 1 (GLP1) is a naturally occurring peptide secreted by intestinal L-cells. Though its primary function is to serve as an incretin, GLP1 reduces gastrointestinal motility. However, only a handful of animal studies have specifically evaluated the influence of GLP1 on colonic motility. Consequently, the aims of this study were to investigate the effects induced by exogenous GLP1, to analyze the mechanism of action, and to verify the presence of GLP1 receptors (GLP1Rs) in human colon circular muscular strips. Organ bath technique, RT-PCR, western blotting, and immunofluorescence were used. In human colon, exogenous GLP1 reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions without affecting the frequency and the resting basal tone. This inhibitory effect was significantly reduced by exendin (9-39), a GLP1R antagonist, which per se significantly increased the spontaneous mechanical activity. Moreover, it was abolished by tetrodotoxin, a neural blocker, or N u -nitro-L-arginine -a blocker of neuronal nitric oxide synthase (nNOS). The biomolecular analysis revealed a genic and protein expression of the GLP1R in the human colon. The double-labeling experiments with anti-neurofilament or anti-nNOS showed, for the first time, that immunoreactivity for the GLP1R was expressed in nitrergic neurons of the myenteric plexus. In conclusion, the results of this study suggest that GLP1R is expressed in the human colon and, once activated by exogenous GLP1, mediates an inhibitory effect on large intestine motility through NO neural release. Key Words " GLP-1 receptor expression " intestinal peptides " colonic motility " nitric oxide Journal of Endocrinology (2014) 221, 29-37 the activation of vagal nerve (Imeryü z et al. 1997, Wettergren et al. 1998) and direct action on the gut wall Journal of Endocrinology
Gut, 1992
Twenty six patients with insulin dependant diabetes meilitus underwent a gastric emptying test, a gail bladder contraction test, an orocaecal transit study, and a colon transit test. Eleven patients had signs of cardiovascular autonomic neuropathy, 15 patients were without signs of cardiovascular autonomic neuropathy. Mean gastric clearance of radioopaque markers ingested with a meal averaged 29-5 (2.3) markers per six hours in subjects without cardiovascular autonomic neuropathy compared with 17*8 (2.3) markers per six hours in patients with cardiovascular autonomic neuropathy (p<002). Gail bladder emptying in response to graded CCK8 stimulation was impaired in five of 11 patients with cardiovascular autonomic neuropathy, whereas it was normal in the patients without cardiovascular autonomic neuropathy (p<0.01). Oral caecal transit times were not significantly different in the two patient groups, whereas colonic transit was slower in the patients with cardiovascular autonomic neuropathy compared with the group without cardiovascular autonomic neuropathy (p<0-02). There was no correlation between disturbed gastric clearance, impaired gall bladder contraction, and prolonged colonic transit time in the patients with cardiovascular autonomic neuropathy nor was there a correlation between any disturbed motor function and age or duration ofdiabetes. It is concluded that autonomic neurophathy can affect motor functions throughout the gastrointestinal tract. Any disturbed motor function in the gut could therefore be one of the numerous expressions of diabetic neuropathy affecting the cardiovascular, the endocrine or the gastrointestinal system.
Enteric neuropathy associated to diabetes mellitus
Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva, 2015
Diabetes mellitus (DM) is a group of diseases highly prevalent nowadays. Its different types produce very similar symptoms with acute and chronic complications. Amongst these, gastrointestinal (GI) dysmotility, associated with the development of neuropathy in the enteric nervous system (ENS) is recognized. The objective is to review the current knowledge on GI dysmotility and enteric neuropathy associated to diabetes mellitus. The different functional and structural alterations within the digestive tract in diabetic patients and animal models are described. Finally, the therapeutic and preventive strategies tested so far in the context of enteric diabetic neuropathy are briefly summarized.In conclusion, amongst the alterations described in DM, the loss of inhibitory intrinsic innervation of the gut is most remarkable. Different therapeutic and/or preventive strategies, including the use of insulin, nerve growth factor or antioxidants, as well as myenteric neuron transplantation, are...