DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells

@article{Masur2006DPPIVIE,
  title={DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells},
  author={K. Masur and F. Schwartz and F. Entschladen and B. Niggemann and K. Zaenker},
  journal={Regulatory Peptides},
  year={2006},
  volume={137},
  pages={147-155}
}
BACKGROUND The glucagon-like peptides-1 and -2 (GLP-1 and -2) are co-secreted after food intake from intestinal L cells. Since both peptides are rapidly degraded by dipeptidyl peptidase-IV (DPPIV), research is focused on the development of DPPIV inhibitors or DPPIV resistant. AIMS In this study we investigated, whether the inhibition of DPPIV activity and the resulting increased half-life of DPPIV substrates may influence cancer development and progression. METHODS We examined proliferation… Expand
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References

SHOWING 1-10 OF 43 REFERENCES
Glucagon-like peptide 2 (GLP-2) accelerates the growth of colonic neoplasms in mice
TLDR
The present results clearly indicate that GLP-2 promotes the growth of mucosal neoplasms and highlight the need for future investigations on the effects of GLp-2 in conditions needing long time treatment or with increased gastrointestinal cancer susceptibility. Expand
Glucagon-Like Peptide 2 Stimulates Intestinal Epithelial Proliferation In Vitro
TLDR
It is suggested that GLP-2 acts directly on human intestinal epithelial cells to stimulate their proliferation, as measured by increased [3H]thymidine incorporation into cellular DNA. Expand
Nutrient-stimulated GLP-2 release and crypt cell proliferation in experimental short bowel syndrome.
TLDR
Glucagon-like peptide-2 is an enteroendocrine peptide that is released in response to luminal nutrients and has unique trophic actions in the gastrointestinal tract and may be important in controlling intestinal adaptation. Expand
Dipeptidyl peptidase inhibitors as new drugs for the treatment of type 2 diabetes
TLDR
Based on their mode of action, DPP-IV inhibitors seem to be of particular value in early forms of type 2 diabetes, either alone or in combination with other types of oral agents. Expand
Glucagon-like peptide (GLP)-2 reduces chemotherapy-associated mortality and enhances cell survival in cells expressing a transfected GLP-2 receptor.
TLDR
It is demonstrated that the antiapoptotic effects of GLP-2 on intestinal crypt cells may be useful for the attenuation of chemotherapy-induced intestinal mucositis. Expand
Teduglutide ([Gly2]GLP‐2) protects small intestinal stem cells from radiation damage
TLDR
The results suggest that teduglutide has the ability to modulate clonogenic stem cell survival in the small intestine and this may have a useful clinical application in the prevention of cancer therapy‐induced mucositis. Expand
Glucagon-like peptide 2: a nutrient-responsive gut growth factor.
TLDR
Based on its efficacy in preventing atrophy and stimulating growth in the neonatal gut, GLP-2 may be a promising therapeutic adjuvant for treatment of infants with compromised gut function. Expand
Glucagon-like peptide-2 enhances intestinal epithelial barrier function of both transcellular and paracellular pathways in the mouse.
TLDR
GLP-2 enhances intestinal epithelial barrier function by affecting both paracellular and transcellular pathways and thus may be of therapeutic value in a number of gastrointestinal conditions. Expand
Glucagon-like peptide 2.
  • D. Drucker
  • Biology, Chemistry
  • The Journal of clinical endocrinology and metabolism
  • 2001
TLDR
The cytoprotective, reparative, and energy-retentive properties of GLp-2 suggests that GLP-2 may potentially be useful for the treatment of human disorders characterized by injury and/or dysfunction of the intestinal mucosal epithelium. Expand
Glucagon-like peptide 2 improves intestinal wound healing through induction of epithelial cell migration in vitro—evidence for a TGF-β-mediated effect
TLDR
In an in vitro model, it was shown that the GLP-2-induced improvement of intestinal wound healing is TGF-β-mediated, and these effects were predominant in the epithelium of the small intestine compared to colonic epithelial cells. Expand
...
1
2
3
4
5
...