Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Target Concepts:
Gene/Protein
Disease
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Query: UMLS:C0021831 (
enteropathy
)
4,403
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The role of circulating factors in regulating colonic stem cells (CoSCs) and colonic epithelial homeostasis is unclear. Individuals with long-standing type 1 diabetes (T1D) frequently have intestinal symptoms, termed diabetic
enteropathy
(DE), though its etiology is unknown. Here, we report that T1D patients with DE exhibit abnormalities in their intestinal mucosa and CoSCs, which fail to generate in vitro mini-guts. Proteomic profiling of T1D+DE patient serum revealed altered levels of insulin-like growth factor 1 (
IGF-I
) and its binding protein 3 (IGFBP3). IGFBP3 prevented in vitro growth of patient-derived organoids via binding its receptor TMEM219, in an
IGF-I
-independent manner, and disrupted in vivo CoSC function in a preclinical DE model. Restoration of normoglycemia in patients with long-standing T1D via kidney-pancreas transplantation or in diabetic mice by treatment with an ecto-TMEM219 recombinant protein normalized circulating
IGF-I
/IGFBP3 levels and reestablished CoSC homeostasis. These findings demonstrate that peripheral
IGF-I
/IGFBP3 controls CoSCs and their dysfunction in DE.
...
PMID:Circulating IGF-I and IGFBP3 Levels Control Human Colonic Stem Cell Function and Are Disrupted in Diabetic Enteropathy. 2648 89
Celiac disease (CD) is a genetically determined gluten-sensitive
enteropathy
resulting in nutrient malabsorption, with an increasing incidence worldwide. In CD children, short stature may be the only presenting clinical feature, even in the absence of gastrointestinal symptoms. Generally, a gluten-free diet (GFD) leads to rapid catch-up growth within 1-2 years. The pathogenesis of CD-associated short stature is still unclear. Besides the involvement of the growth hormone (GH)/
IGF-I
axis, other pathogenetic mechanisms may include autoimmune disorders of the pituitary gland and altered ghrelin secretion. Furthermore, some CD patients do not show catch-up growth during a GFD, despite reversion to seronegativity for CD markers. These subjects may have GH deficiency and could benefit from GH therapy. This review deals with the problem of linear growth in CD children and points to the importance of the evaluation of GH secretion in those children who show no catch-up growth after the introduction of a GFD.
...
PMID:Celiac disease and short stature in children. 3073 15