CoChat
Sign Up
Cited by 98Gastrointestinal motility and disordersCongenital gastrointestinal and neural anomaliesPancreatic function and diabetes

Reduced Insulin and IGF-I Signaling, not Hyperglycemia, Underlies the Diabetes-Associated Depletion of Interstitial Cells of Cajal in the Murine Stomach

Open access
Horváth, Viktor J., Vittal, Harsha, Ördög, Tamás·2005·Diabetes
DOI 10.2337/diabetes.54.5.1528
Open this paper in CoChat — free accountOpen PDF

Abstract

Damage to interstitial cells of Cajal (ICC), pacemakers, and mediators of neuromuscular neurotransmission in the gastrointestinal tract contributes to the pathogenesis of diabetic gastroenteropathy in both patients and animal models. ICC depletion in diabetes may result from chronic hyperglycemia or lost/ineffective insulin signaling. Because independent control of insulin and glucose concentrations is difficult in chronic in vivo studies, we used long-term organotypic cultures to address this problem. Murine gastric muscles were cultured in normoglycemic or hyperglycemic basal media with or without insulin or IGF-I for 1–3 months, the time required for gastroparesis and ICC damage to develop in diabetic mice. ICC were assessed by c-Kit immunohistochemistry and quantitative analysis of c-kit expression. Electrical pacemaking was studied by intracellular recording of slow waves. ICC survived for at least 34 days in unsupplemented normoglycemic media, but their networks, c-kit expression, and slow waves were profoundly reduced after 68 days. These changes could be entirely prevented by insulin or IGF-I supplementation. ICC networks were completely resistant to hyperglycemia for at least 72 days. Thus, hyperglycemia is unlikely to be responsible for the diabetes-associated depletion of ICC. In contrast, maintenance of ICC requires insulin or IGF-I, which are reduced or ineffective in diabetes.

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 · 10.2337/diabetes.54.5.1528

Cites

32 of 32 references verified0 citation errors · 0 not checkable

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?

  • In diabetes, chronic hyperglycemia and reduced trophic factors, in particular the reduction of KIT/stem cell factor (SCF), cause the loss or dysfunction of ICCs, leading to dysregulated gastric emptying.

    “In diabetes, chronic hyperglycemia, and reduced trophic factors, in particular the reduction of KIT/stem cell factor (SCF), cause the loss or dysfunction of ICCs [52], leading to dysregulated gastric emptying [4, 19, 53].”

    From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [52]

    The Results and Discussion (pp. 3–4) report that long-term hyperglycemia did not damage ICC networks; insulin or IGF-I prevented their depletion. The Discussion (p. 4) mentions stem cell factor only as a possible mediator of insulin’s effects, not as a demonstrated factor reduced in diabetes. The paper therefore contradicts the claim that chronic hyperglycemia causes ICC loss and does not establish the claimed SCF mechanism. (LLM, conf=0.89)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • In diabetes, insulin and IGF-1 deficiency causes muscle atrophy and reduced SCF production, leading to ICC depletion and impaired neuromuscular transmission.

    “In diabetes, insulin and IGF-1 deficiency causes muscle atrophy and reduced SCF production, leading to ICC depletion and impaired neuromuscular transmission [52–60].”

    From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [52]

    The summary (p. 1) and Discussion (pp. 4–5) support a role for reduced or ineffective insulin and IGF-I signaling in gastric ICC depletion; the paper also identifies ICC as mediators of neuromuscular neurotransmission. The Discussion (p. 4) says SCF is important for ICC maintenance but only suggests that its endogenous production may depend on additional factors. It does not establish the claimed sequence of muscle atrophy causing reduced SCF production and then ICC depletion. (LLM, conf=0.86)

    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

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Horváth, V. J., Vittal, H., & Ördög, T.
Affiliations
  • Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, Nevada
  • University of Nevada, Reno (US)
Venue
Diabetes
Publisher
American Diabetes Association
Published
2005-05-01
Volume
54
Issue
5
Pages
1528-1533
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.54.5.1528
OpenAlex
W2112099477
Cited by
98
References
32
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2023: 7 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 3 · 2014: 9 · 2013: 4 · 2012: 3
FWCI
6.90
Type
journal article
Language
en
Open access
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (P01DK041315, R01DK058185, DK 58185, DK41315)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
interstitial cells of Cajal, diabetic gastroparesis, insulin signaling, insulin-like growth factor I, hyperglycemia, slow waves, c-kit expression, organotypic culture, gastric smooth muscle
MeSH terms
Animals, Diabetes Mellitus, Hyperglycemia, Insulin, Insulin-Like Growth Factor I, Mice, Inbred BALB C, Organ Culture Techniques, Stomach, Signal Transduction, Muscle, Skeletal, Mice

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