scholarly journals Impaired insulin/IGF-1 is responsible for diabetic gastroparesis by damaging myenteric cholinergic neurones and interstitial cells of Cajal

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Shu Yang ◽  
Bo Wu ◽  
Haimei Sun ◽  
Tingyi Sun ◽  
Kai Han ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Interstitial Cells Of Cajal ◽  
Serum Insulin ◽  
Smooth Muscles ◽  
Interstitial Cells ◽  
Diabetic Gastroparesis ◽  
Cholinergic Neurones ◽  
Cells Of Cajal ◽  
Type 1 Dm

Diabetic gastroparesis is a common complication of diabetes mellitus (DM) that is characterized by decreased serum insulin and insulin-like growth factor-1 (IGF-1). Despite the fact that insulin treatment not glycemic control potently accelerated gastric emptying in type 1 DM patients, the role of insulin/InsR and IGF-1/IGF-1R signaling in diabetic gastroparesis remains incompletely elucidated. In the present study, type 1 DM mice were established and treated with insulin or Voglibose for 8 weeks. The gastric emptying was delayed from DM week 4 when the gastric InsR and IGF-1R were declined. Meanwhile, the gastric choline acetyltransferase (ChAT) was significantly reduced and the myenteric cholinergic neurones and their fibers were significantly diminished. The production of stem cell factor (SCF) was dramatically repressed in the gastric smooth muscles in DM week 6. TWereafter, interstitial cells of Cajal (ICC) were clearly lost and their networks were impaired in DM week 8. Significantly, compared with Voglibose, an 8-week treatment with insulin more efficiently delayed diabetic gastroparesis development by protecting the myenteric cholinergic neurones and ICC. In conclusion, diabetic gastroparesis was an aggressive process due to the successive damages of myenteric cholinergic neurones and ICC by impairing the insulin/InsR and IGF-1/IGF-1R signaling. Insulin therapy in the early stage may delay diabetic gastroparesis.

scholarly journals Hyperglycemia in the early stages of type 1 diabetes accelerates gastric emptying through increased networks of interstitial cells of Cajal

PLoS ONE ◽  
2019 ◽  
Vol 14 (10) ◽  
pp. e0222961 ◽  
Author(s):  
Kazuhisa Kishi ◽  
Noriyuki Kaji ◽  
Tamaki Kurosawa ◽  
Satoshi Aikiyo ◽  
Masatoshi Hori
Keyword(s):  
Type 1 Diabetes ◽  
Gastric Emptying ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Early Stages ◽  
Cells Of Cajal

scholarly journals Electroacupuncture Relieves Suppression of Autophagy in Interstitial Cells of Cajal of Diabetic Gastroparesis Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xing Wei ◽  
Yaping Lin ◽  
Dongfeng Zhao ◽  
Xiaojuan Xiao ◽  
Qiao Chen ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Gastric Emptying ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Diabetic Gastroparesis ◽  
Control Group ◽  
Autophagy Flux ◽  
Gastric Emptying Rate ◽  
Modeling Group ◽  
Cells Of Cajal

Background. The incidence of diabetic gastroparesis (DGP) is mainly blamed to abnormity of interstitial cells of Cajal (ICCs). Autophagy could degrade damaged proteins and organelles to keep intracellular homeostasis, and it could directly influence structure and number of cells. In this study, we aimed to figure out the relationship between DGP and autophagy of ICCs. Methods. Sixty Sprague-Dawley (SD) rats were randomly divided into normal control group (NC, 10) and modeling group (50). Rats in the modeling group were injected 2% streptozotocin (STZ) and fed with high-glucose and high-fat diet for 8 weeks in order to establish DGP rat model. After modeling, 30 successfully modeled rats were randomly selected and separated into diabetic gastroparesis group (DGP, 10), GDP rats with electroacupuncture group (EA, 10), and GDP rats with metoclopramide group (MP, 10). When the intervention was completed, blood glucose was measured by ONE TOUCH glucometer and gastrointestinal propulsive rate was detected through measuring optical density. Autophagosomes were observed under transmission electron microscope (TEM). The expression of LC3 protein and P62 protein was measured by Western blot. When ICCs were transfected with GFP-RFP-LC3 plasmid, autophagy flux was observed by laser scanning confocal microscope. Results. (1) After intervention, compared with blood glucose of rats in the NC group, all of the DGP, EA, and MP groups were remarkably increased (P<0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P<0.01). (2) Compared with gastrointestinal propulsive rate of rats in the NC group, no matter gastric emptying rate or intestinal propulsive rate, the EA and MP groups were significantly reduced (P<0.01); compared with the NC group, gastric emptying rate and intestinal propulsive rate in the EA group were obviously decreased (P<0.05, P<0.01); compared with the DGP group, the EA and MP groups were increased significantly (P<0.01). (3) Compared with the NC group, intensity of RFP and GFP in the DGP group was obviously increased (P<0.05, P<0.01), in other words, the DGP group accompanying suppression of autophagy; compared with the DGP group, intensity of RFP and GFP in the EA group was decreased significantly (P<0.05, P<0.01). (4) There was no autophagosome in the NC group, and an autophagosome existed in the DGP group. Both EA and MP groups found autophagy. (5) When coming to LC3 II/LC3 I, compared with the NC group, the ratio was enhanced in the DGP and EA groups (P<0.01, P<0.05); compared with the DGP group, LC3 II/LC3 I was dramatically decreased in the MP and EA groups (P<0.01). (6) As the substrate of degradation, the expression of P62 in the other three groups was significantly increased (P<0.01) compared with the NC group; compared with the DGP group, the amount of P62 in the EA and MP groups was reduced greatly (P<0.01). Conclusion. The impaired autophagy flux in ICCs is the pathological basis of diabetic gastroparesis, blaming to fusion dysfunction of autophagosome and lysosome and electroacupuncture (EA) could ease the suppression of autophagy to improve gastric motility.

Succinate Accumulation Epigenetically Represses Kit Expression, Reduces Interstitial Cells of Cajal (ICC) and Delays Gastric Emptying of Solids

2017 ◽  
Vol 152 (5) ◽  
pp. S129-S130
Author(s):  
Siva Arumugam Saravanaperumal ◽  
Yujiro Hayashi ◽  
Gabriella B. Gajdos ◽  
Sabriya A. Syed ◽  
Chad R. Clark ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Cells Of Cajal

Distribution of Interstitial Cells of Cajal in the Internal Anal Sphincter of Patients With Internal Anal Sphincter Achalasia and Hirschsprung Disease

2003 ◽  
Vol 127 (9) ◽  
pp. 1192-1195 ◽  
Author(s):  
Anna Piaseczna Piotrowska ◽  
Valeria Solari ◽  
Prem Puri
Keyword(s):  
Anal Sphincter ◽  
Internal Anal Sphincter ◽  
Interstitial Cells Of Cajal ◽  
Internal Sphincter ◽  
Smooth Muscles ◽  
Hirschsprung Disease ◽  
Interstitial Cells ◽  
Nerve Fibers ◽  
Internal Anal Sphincter Achalasia ◽  
Cells Of Cajal

Abstract Context.—Interstitial cells of Cajal (ICCs) are pacemaker cells in the smooth muscles of the gut. The internal anal sphincter (IAS) is the most caudal part of gastrointestinal tract. It has the important function of maintaining fecal continence. It has been proposed that ICCs in the IAS mediate the inhibitory innervation of the recto-anal reflexes. Objective.—To investigate the distribution of ICCs in the normal IAS and in the IAS of children diagnosed with internal anal sphincter achalasia (IASA) and Hirschsprung disease (HD). Methods.—At the time of IAS myectomy, specimens of the IAS were taken from 8 patients with IASA, 4 patients with HD, and 4 normal controls. All specimens were examined using anti–c-Kit and antiperipherin antibodies; immunolocalization was detected with light microscopy. Density of the ICCs was graded by computerized image analysis. Results.—There was strong peripherin immunoreactivity in the ganglia cells and nerve fibers in the normal IAS. The number of peripherin-positive nerve fibers was markedly reduced in the IAS in patients with IASA. In HD patients, there was lack of peripherin immunoreactivity in the IAS, but hypertrophic nerve trunks stained strongly. Many c-Kit–positive ICCs were present among the muscle fibers and between the muscle bundles in the normal IAS. In HD and IASA patients, ICCs were absent or markedly reduced. Conclusion.—Altered distribution of ICCs in the internal sphincter in IASA and HD may contribute to motility dysfunction in these patients.

Proteins of interstitial cells of Cajal and intestinal smooth muscle, colocalized with caveolin-1

2005 ◽  
Vol 288 (3) ◽  
pp. G571-G585 ◽  
Author(s):  
Woo Jung Cho ◽  
E. E. Daniel
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Gap Junction ◽  
Interstitial Cells Of Cajal ◽  
Smooth Muscles ◽  
Circular Muscle ◽  
Interstitial Cells ◽  
Caveolin 1 ◽  
Cells Of Cajal ◽  
Junction Proteins

The murine jejunum and lower esophageal sphincter (LES) were examined to determine the locations of various signaling molecules and their colocalization with caveolin-1 and one another. Caveolin-1 was present in punctate sites of the plasma membranes (PM) of all smooth muscles and diffusely in all classes of interstitial cells of Cajal (ICC; identified by c-kit immunoreactivity), ICC-myenteric plexus (MP), ICC-deep muscular plexus (DMP), ICC-serosa (ICC-S), and ICC-intramuscularis (IM). In general, all ICC also contained the L-type Ca2+ (L-Ca2+) channel, the PM Ca2+ pump, and the Na+/Ca2+ exchanger-1 localized with caveolin-1. ICC in various sites also contained Ca2+-sequestering molecules such as calreticulin and calsequestrin. Calreticulin was present also in smooth muscle, frequently in the cytosol, whereas calsequestrin was present in skeletal muscle of the esophagus. Gap junction proteins connexin-43 and -40 were present in circular muscle of jejunum but not in longitudinal muscle or in LES. In some cases, these proteins were associated with ICC-DMP. The large-conductance Ca2+-activated K+ channel was present in smooth muscle and skeletal muscle of esophagus and some ICC but was not colocalized with caveolin-1. These findings suggest that all ICC have several Ca2+-handling and -sequestering molecules, although the functions of only the L-Ca2+ channel are currently known. They also suggest that gap junction proteins are located at sites where ultrastructural gap junctions are know to exist in circular muscle of intestine but not in other smooth muscles. These findings also point to the need to evaluate the function of Ca2+ sequestration in ICC.

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