CoChat
Sign Up
Cited by 123Gastrointestinal motility and disordersGastroesophageal reflux and treatmentsCongenital gastrointestinal and neural anomalies

Ultrastructural differences between diabetic and idiopathic gastroparesis

Open access
Faussone‐Pellegrini, Maria Simonetta, Grover, Madhusudan, Pasricha, Pankaj J., Bernard, Cheryl E., Lurken, Matthew S., Smyrk, Thomas C., Parkman, Henry P., Abell, Thomas L. +11 more·2012·Journal of Cellular and Molecular Medicine
DOI 10.1111/j.1582-4934.2011.01451.xPMC PMC3250562
Open this paper in CoChat — free accountOpen PDF

Abstract

The ultrastructural changes in diabetic and idiopathic gastroparesis are not well studied and it is not known whether there are different defects in the two disorders. As part of the Gastroparesis Clinical Research Consortium, full thickness gastric body biopsies from 20 diabetic and 20 idiopathic gastroparetics were studied by light microscopy. Abnormalities were found in many (83%) but not all patients. Among the common defects were loss of interstitial cells of Cajal (ICC) and neural abnormalities. No distinguishing features were seen between diabetic and idiopathic gastroparesis. Our aim was to provide a detailed description of the ultrastructural abnormalities, compare findings between diabetic and idiopathic gastroparesis and determine if patients with apparently normal immunohistological features have ultrastructural abnormalities. Tissues from 40 gastroparetic patients and 24 age‐ and sex‐matched controls were examined by transmission electron microscopy (TEM). Interstitial cells of Cajal showing changes suggestive of injury, large and empty nerve endings, presence of lipofuscin and lamellar bodies in the smooth muscle cells were found in all patients. However, the ultrastructural changes in ICC and nerves differed between diabetic and idiopathic gastroparesis and were more severe in idiopathic gastroparesis. A thickened basal lamina around smooth muscle cells and nerves was characteristic of diabetic gastroparesis whereas idiopathic gastroparetics had fibrosis, especially around the nerves. In conclusion, in all the patients TEM showed abnormalities in ICC, nerves and smooth muscle consistent with the delay in gastric emptying. The significant differences found between diabetic and idiopathic gastroparesis offers insight into pathophysiology as well as into potential targeted therapies.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/j.1582-4934.2011.01451.x

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Advanced diabetic gastroparesis can be associated with smooth-muscle degeneration, fibrosis, collagen deposition, and ultrastructural abnormalities such as thickened basal lamina, changes that likely contribute to a hypocontractile phenotype and delayed gastric emptying.

    “Moreover, advanced diabetic gastroparesis can be associated with smooth-muscle degeneration, fibrosis, collagen deposition, and ultrastructural abnormalities such as thickened basal lamina, changes that likely contribute to a hypocontractile phenotype and delayed gastric emptying [23, 42–45].”

    From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [45]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 30

  1. [1]Farrell FJ Keeffe EB Diabetic gastroparesis Dig Dis 1995 13 291 300 8542664
  2. [2]Stanciu GO Gastroparesis and its management Rev Med Chir Soc Med Nat Iasi 2001 105 451 6 12092172
  3. [3]Choi KM Gibbons SJ Nguyen TV Heme oxygenase-1 protects interstitial cells of Cajal from oxidative stress and reverses diabetic gastroparesis Gastroenterology 2008 135 2055 64, 2064 e1-2 18926825 PMC2796242
  4. [4]Horvath VJ Vittal H Lorincz A Reduced stem cell factor links smooth myopathy and loss of interstitial cells of Cajal in murine diabetic gastroparesis Gastroenterology 2006 130 759 70 16530517
  5. [5]Ordog T Takayama I Cheung WK Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis Diabetes 2000 49 1731 9 11016458
  6. [6]Spangeus A El-Salhy M Myenteric plexus of obese diabetic mice (an animal model of human type 2 diabetes) Histol Histopathol 2001 16 159 65 11193191
  7. [7]Spangeus A Suhr O El-Salhy M Diabetic state affects the innervation of gut in an animal model of human type 1 diabetes Histol Histopathol 2000 15 739 44 10963118
  8. [8]Takahashi T Nakamura K Itoh H Impaired expression of nitric oxide synthase in the gastric myenteric plexus of spontaneously diabetic rats Gastroenterology 1997 113 1535 44 9352855
  9. [9]Vittal H Farrugia G Gomez G Mechanisms of disease: the pathological basis of gastroparesis-a review of experimental and clinical studies Nat Clin Pract Gastroenterol Hepatol 2007 4 336 46 17541447
  10. [10]Wang XY Huizinga JD Diamond J Loss of intramuscular and submuscular interstitial cells of Cajal and associated enteric nerves is related to decreased gastric emptying in streptozotocin-induced diabetes Neurogastroenterol Motil 2009 21 1095 e92 19566589
  11. [11]Battaglia E Bassotti G Bellone G Loss of interstitial cells of Cajal network in severe idiopathic gastroparesis World J Gastroenterol 2006 12 6172 7 17036390 PMC4088112
  12. [12]Ejskjaer NT Bradley JL Buxton-Thomas MS Novel surgical treatment and gastric pathology in diabetic gastroparesis Diabet Med 1999 16 488 95 10391397
  13. [13]Forster J Damjanov I Lin Z Absence of the interstitial cells of Cajal in patients with gastroparesis and correlation with clinical findings J Gastrointest Surg 2005 9 102 8 15623450
  14. [14]Harberson J Thomas RM Harbison SP Gastric neuromuscular pathology in gastroparesis: analysis of full-thickness antral biopsies Dig Dis Sci 2010 55 359 70 19997975
  15. [15]He CL Soffer EE Ferris CD Loss of interstitial cells of Cajal and inhibitory innervation in insulin-dependent diabetes Gastroenterology 2001 121 427 34 11487552
  16. [16]Iwasaki H Kajimura M Osawa S 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 J Gastroenterol 2006 41 1076 87 17160518
  17. [17]Lin Z Sarosiek I Forster J Association of the status of interstitial cells of Cajal and electrogastrogram parameters, gastric emptying and symptoms in patients with gastroparesis Neurogastroenterol Motil 2010 22 56 61 19614868
  18. [18]Miller SM Narasimhan RA Schmalz PF Distribution of interstitial cells of Cajal and nitrergic neurons in normal and diabetic human appendix Neurogastroenterol Motil 2008 20 349 57 18069951
  19. [19]Pasricha PJ Pehlivanov ND Gomez G Changes in the gastric enteric nervous system and muscle: a case report on two patients with diabetic gastroparesis BMC Gastroenterol 2008 8 21 18513423 PMC2442096
  20. [20]Sokol H Lavergne-Slove A Mikol J Severe isolated myopathic gastroparesis: a case report with pathological findings Gut 2006 55 1662 17047114 PMC1860088
  21. [21]Zarate N Mearin F Wang XY Severe idiopathic gastroparesis due to neuronal and interstitial cells of Cajal degeneration: pathological findings and management Gut 2003 52 966 70 12801952 PMC1773724
  22. [22]Grover M Farrugia G Lurken MS Cellular changes in diabetic and idiopathic gastroparesis Gastroenterology 2011 140 1575 85 21300066 PMC3081914
  23. [23]Faussone-Pellegrini MS Pantalone D Cortesini C An ultrastructural study of the smooth muscle cells and nerve endings of the human stomach J Submicrosc Cytol Pathol 1989 21 421 37 2790730
  24. [24]Faussone-Pellegrini MS Pantalone D Cortesini C An ultrastructural study of the interstitial cells of Cajal of the human stomach J Submicrosc Cytol Pathol 1989 21 439 60 2790731
  25. [25]Farrugia G Interstitial cells of Cajal in health and disease Neurogastroenterol Motil 2008 20 Suppl 1 54 63 18402642
  26. [26]Yoshida MM Schuffler MD Sumi SM There are no morphologic abnormalities of the gastric wall or abdominal vagus in patients with diabetic gastroparesis Gastroenterology 1988 94 907 14 3345891
  27. [27]Gibbons SJ De Giorgio R Pellegrini MS Apoptotic cell death of human interstitial cells of Cajal Neurogastroenterol Motil 2009 21 85 93 18798796 PMC2627790
  28. [28]Tharayil VS Wouters MM Stanich JE Lack of serotonin 5-HT2B receptor alters proliferation and network volume of interstitial cells of Cajal in vivo Neurogastroenterol Motil 2010 22 462 9 19941613 PMC2852486
  29. [29]Choi KM Kashyap PC Dutta N CD206-positive M2 macrophages that express heme oxygenase-1 protect against diabetic gastroparesis in mice Gastroenterology 2010 138 2399 409, 2409 e1 20178793 PMC2883675
  30. [30]Watkins CC Sawa A Jaffrey S Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy J Clin Invest 2000 106 373 84 10930440 PMC314323

Cited by

Sorted by citations

Authors
Faussone‐Pellegrini, M. S., Grover, M., Pasricha, P. J., Bernard, C. E., Lurken, M. S., Smyrk, T. C., Parkman, H. P., Abell, T. L., Snape, W. J., Hasler, W. L., Ünalp‐Arida, A., Nguyen, L., Koch, K. L., Calles, J., Lee, L., Tonascia, J., Hamilton, F. A., Farrugia, G., & for The NIDDK Gastroparesis Clinical Research Consortium (GpCRC)
Affiliations
  • University of Florence (IT)
  • Mayo Clinic (US)
  • Stanford University (US)
  • Temple University (US)
  • University of Mississippi (US)
  • California Pacific Medical Center (US)
  • University of Michigan (US)
  • Wake Forest University (US)
  • Johns Hopkins University (US)
  • National Institutes of Health (US)
Corresponding author
Farrugia, Gianrico
ORCID
Venue
Journal of Cellular and Molecular Medicine
Publisher
Wiley
Published
2012-06-28
Volume
16
Issue
7
Pages
1573-1581
ISSN
  • 1582-1838 (ISSN-L)
  • 1582-4934
DOI
10.1111/j.1582-4934.2011.01451.x
PMC
PMC3250562
OpenAlex
W2079670285
Cited by
123
References
0
Citations by year
2026: 5 · 2025: 8 · 2024: 4 · 2023: 8 · 2022: 7 · 2021: 10 · 2020: 8 · 2019: 12 · 2018: 10 · 2017: 6 · 2016: 10 · 2015: 8 · 2014: 13 · 2013: 8 · 2012: 6
FWCI
8.86
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Cellular and Molecular Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Deep Blue (University of Michigan) (submittedVersion)
Funders
  • Wake Forest University
  • Johns Hopkins University
  • Johns Hopkins Bloomberg School of Public Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (U01DK074008, DK57061, DK-68055, U01DK073985, P01DK068055, PO1 DK68055, DK 84567, U01DK073974, R01DK057061, P30DK084567, U01DK074007, U01DK073983, U01DK073975, U01DK074035, P01-DK-68055)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
  • Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
Keywords
diabetic gastroparesis, idiopathic gastroparesis, interstitial cells of Cajal, gastric smooth muscle, lipofuscin, lamellar bodies, basal lamina thickening, nerve fibrosis, delayed gastric emptying
MeSH terms
Adult, Aged, Diabetes Mellitus, Diabetic Neuropathies, Female, Gastric Emptying, Humans, Male, Middle Aged, Stomach, Case-Control Studies, Gastroparesis, Microscopy, Electron, Transmission, Interstitial Cells of Cajal

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review