Effect of porcine glucagon‐like peptides‐2 on tight junction in GLP‐2R + IPEC‐J2 cell through the PI₃k/Akt/mTOR/p70^S6K signalling pathway

Abstract

Because of rare glucagon-like peptide-2 (GLP-2) receptor (+) cells within the gut mucosa, the molecular mechanisms transducing the diverse actions of GLP-2 remain largely obscure. This research identified the naturally occurring intestinal cell lines that endogenously express GLP-2R and determined the molecular mechanisms of the protective effects of GLP-2-mediated tight junctions (TJ) in GLP-2R (+) cell line. (i) Immunohistochemistry results showed that GLP-2R is localised to the epithelia, laminae propriae and muscle layers of the small and large bowels of newborn piglets. (ii) GLP-2R expression was apparent in the cytoplasm of endocrine cells in IPEC-J2 cell lines. (iii) The protein expressions of ZO-1, claudin-1, occludin, p-PI K, p-Akt, p-mTOR and p-p70 significantly (p < 0.05) increased in GLP-2-treated IPEC-J2 cells, and all of them significantly (p < 0.05) decreased when LY-294002 or rapamycin was added. GLP-2 improves intestinal TJ expression of GLP-2R (+) cells through the PI k/Akt/mTOR/p70 signalling pathway.

Flaccidoxide Induces Apoptosis Through Down-regulation of PI3K/AKT/mTOR/p70S6K Signaling in Human Bladder Cancer Cells

“…p70S6K is a downstream target of mTOR kinase (32), and studies have demonstrated that p-mTOR activates p-p706S kinase, leading to p-S6 activation (33,34). Our results showed that flaccidoxide-treated cells had lower expression levels of p-mTOR, as well as reduced expression of its downstream targets, p-p706SK, p-S6 and p-eIF4B.…”

Effects of Glucagon-Like Peptide-2-Expressing Saccharomyces cerevisiae Not Different from Empty Vector

“…GLP-2 supplementation has not yet been employed to modify intestinal microbiotas, but most studies have primarily focused on investigating the effects of GLP-2 on the regulation of intestinal growth and functions [5,17,18]. Fig.…”

Effects of glepaglutide, a long‐acting glucagon‐like peptide‐2 analog, on intestinal morphology and perfusion in patients with short bowel syndrome: Findings from a randomized phase 2 trial

“…25,26 Moreover, several animal studies have demonstrated that treatment with GLP-2 can improve intestinal barrier function by reducing the gastrointestinal permeability and increasing key markers of tight-junction integrity. 21,27,28 Exogenous GLP-2 has also been shown to stimulate proximal intestinal blood flow, 20 increase the overall splanchnic oxygenation 29 and angiogenesis, 30,31 as well as promote intestinal mucosal growth, 22 thereby enhancing postresectional adaptation. This has been demonstrated to enhance fluid and nutrient absorption as well as reduce malabsorption and diarrhea in both preclinical and clinical SBS settings.…”

“…Thus, plasma citrulline, a proposed marker of enterocyte mass, has also been shown to increase in humans following treatment with GLP‐2 25,26 . Moreover, several animal studies have demonstrated that treatment with GLP‐2 can improve intestinal barrier function by reducing the gastrointestinal permeability and increasing key markers of tight‐junction integrity 21,27,28 …”

“… 25 , 26 Moreover, several animal studies have demonstrated that treatment with GLP‐2 can improve intestinal barrier function by reducing the gastrointestinal permeability and increasing key markers of tight‐junction integrity. 21 , 27 , 28 …”