A deficiency of gastric interstitial cells of Cajal accompanied by decreased expression of neuronal nitric oxide synthase and substance P in patients with type 2 diabetes mellitus

Iwasaki, Hirohiko; Kajimura, Masayoshi; Osawa, Satoshi; Kanaoka, Shigeru; Furuta, Takahisa; Ikuma, Mutsuhiro; Hishida, Akira

doi:10.1007/s00535-006-1909-8

Cited by 171 publications

(176 citation statements)

References 44 publications

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“…The cytoplasm was partially dissolved, there were fewer organelles and a number of autophagic vacuoles could be observed within the cytoplasm. The reduction in the number of organelles within the ICCs was consistent with the literature (3,4,7,17).In addition, the peripheral axons and dendrites were partially swollen or dissolved, the electron density was not uniform, and vacuoles had formed. The synaptic vesicle content inside the nerve varicosity was significantly reduced, and the number of gastric ICCs was significantly decreased compared with the blank group.…”

Section: Discussionsupporting

confidence: 90%

“…Between 30 and 50% of patients that have had diabetes for >10 years exhibit such symptoms of gastric neuromuscular dysfunction as satiety, weight loss, abdominal pain, distension and discomfort, nausea and vomiting. Neuropathological changes, a reduction in the number of gastrointestinal interstitial cells of Cajal (ICCs), morphological changes, hyperglycemia, microvascular diseases, microcirculatory disorders, gastrointestinal hormone changes and Helicobacter pylori are all believed to be involved in the pathogenesis of diabetic gastroparesis (DGP) (1)(2)(3)(4)(5)(6)(7). The inherent gastric nerves have recently been subject to significant focus, and it has been suggested that the most important mechanism of DGP is the deficiency of neuronal nitric oxide synthase expression and the reduction of ICCs (1)(2)(3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

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Effect of electroacupuncture on gastric interstitial cells of Cajal in a rat model of diabetic gastroparesis

Lin

Zhang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to observe the effect of electroacupuncture (EA) on the gastric interstitial cells of Cajal (ICCs) in a rat model of diabetic gastroparesis (DGP). The gastric tissues were collected from 75 rats, which had been divided into three equal groups (n=25/group): Blank, model and EA. Hematoxylin and eosin and immunohistochemical staining were used to observe the cellular morphology and distribution of c-kit-positive gastric ICCs; light microscopy was used to count the number of ICCs; and electron microscopy was used to observe the ultrastructure of the rat ICCs. Compared with the model group, the gastromucosal glandular and smooth muscle cells of the EA group were more regularly arranged, with fewer vacuoles; there was an increased cellular gap and the vacuolar degeneration on the gastric walls was mild. Image analysis showed that the blank group exhibited the greatest number of c-kit-positive ICCs, and the number of c-kit-positive ICCs in the blank group was significantly different from that in the model and EA groups (P<0.01): Blank group > EA group > model group. In conclusion, DGP rats exhibited a reduced number of gastric ICCs, altered ultrastructural morphology and a reduced number of cell organelles, particularly mitochondria, compared with the blank group. EA may help to reverse the various pathological changes of gastric ICCs in rat models of DGP.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Effect of electroacupuncture on gastric interstitial cells of Cajal in a rat model of diabetic gastroparesis

Lin

Zhang

et al. 2016

Experimental and Therapeutic Medicine

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“…Recently, the ICC, which is known to regulate spontaneous contraction by generating slow waves in the smooth muscle of the gastrointestinal tract, has been increasingly studied. 17,[26][27][28][29][30][31][32][33][34][35][36] Many studies have reported that ICC injury plays an important role in various chronic diseases that cause abnormal gastrointestinal contractions. 27,[29][30][31][32][33]35 In addition, it has been reported that spontaneous contraction signals are transmitted by ICC networks and that the loss of small intestinal motility in humans was caused by reduction in the ICC networks.…”

Section: Discussionmentioning

confidence: 99%

Alterations of Colonic Contractility in an Interleukin-10 Knockout Mouse Model of Inflammatory Bowel Disease

Park

Kwon

Kim

et al. 2015

J Neurogastroenterol Motil

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Background/Aims Inflammatory bowel disease is commonly accompanied by colonic dysmotility and causes changes in intestinal smooth muscle contractility. In this study, colonic smooth muscle contractility in a chronic inflammatory condition was investigated using smooth muscle tissues prepared from interleukin-10 knockout (IL-10 −/− ) mice. Methods Prepared smooth muscle sections were placed in an organ bath system. Cholinergic and nitrergic neuronal responses were observed using carbachol and electrical field stimulation with L-NG-nitroarginine methyl ester (L-NAME). The expression of interstitial cells of Cajal (ICC) networks, muscarinic receptors, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) was observed via immunofluorescent staining. Results The spontaneous contractility and expression of ICC networks in the proximal and distal colon was significantly decreased in IL-10 −/− mice compared to IL-10 +/+ mice. The contractility in response to carbachol was significantly decreased in the proximal colon of IL-10 −/− mice compared to IL-10 +/+ mice, but no significant difference was found in the distal colon. In addition, the expression of muscarinic receptor type 2 was reduced in the proximal colon of IL-10 −/− mice. The nictric oxide-mediated relaxation after electrical field stimulation was significantly decreased in the proximal and distal colon of IL-10 −/− mice. In inflamed colon, the expression of nNOS decreased, whereas the expression of iNOS increased. Conclusions These results suggest that damage to the ICC network and NOS system in the proximal and distal colon, as well as damage to the smooth muscle cholinergic receptor in the proximal colon may play an important role in the dysmotility of the inflamed colon.

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“…A relative loss of ICC in colonic surgical specimens from children with congenital aganglionosis of Hirschsprung's disease was reported 29,31 . Decreased populations of ICC were observed in chronic idiopathic intestinal pseudoobstruction 15,26 , slow-transit constipation 12,13,20,29,30 , and also in diabetic gastroenteropathy 13,16 . Hagger et al 11 , Geraldino et al 8 , and Iantorno et al 14 have demonstrated a reduction of ICC in the resected colon or in colonic biopsies in Chagasic patients with megacolon compared to the colon of non-Chagasic patients.…”

Section: Discussionmentioning

confidence: 98%

Depopulation of interstitial cells of cajal in chagasic megacolon: towards tailored surgery?

Araújo

Dumarco

Rawet

et al. 2010

ABCD, arq. bras. cir. dig.

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-Background -The mechanism of constipation in patients with Chagasic megacolon remains partially explained. In these patients, it was recently demonstrated a reduction in the population of interstitial cells of Cajal. Aim -To evaluate density of Cajal cells in the surgically resected colon of Chagasic patients in comparison to control patients, and to verify possible association between preoperative and postoperative bowel function of Chagasic patients and colonic cell count. Method -Sixteen patients with Chagasic megacolon were operated on. Clinical pre-and postoperative evaluation using the Cleveland Clinic Constipation Score was undertaken.Resected colons were examined. Cajal cells were identified by immunohistochemistry using anti-CD117 antibody. The mean cell number was compared to resected colons from 16 patients with non-obstructive sigmoid cancer. Association between preand post-operative constipation scores and cell count for megacolon patients was evaluated using the Pearson coefficient correlation test (r).

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A deficiency of gastric interstitial cells of Cajal accompanied by decreased expression of neuronal nitric oxide synthase and substance P in patients with type 2 diabetes mellitus

Abstract: These results suggest that lower gastric ICC, nNOS, and SP densities in patients with DM may be associated with the pathogenesis of diabetic gastroparesis.

Cited by 171 publications

References 44 publications

Effect of electroacupuncture on gastric interstitial cells of Cajal in a rat model of diabetic gastroparesis

Effect of electroacupuncture on gastric interstitial cells of Cajal in a rat model of diabetic gastroparesis

Alterations of Colonic Contractility in an Interleukin-10 Knockout Mouse Model of Inflammatory Bowel Disease

Depopulation of interstitial cells of cajal in chagasic megacolon: towards tailored surgery?

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