Effects of PEGylated porcine glucagon-like peptide-2 therapy in weaning piglets challenged with lipopolysaccharide

Glucagon-like peptide 2 and its beneficial effects on gut function and health in production animals

“…In addition, Yu et al [105] demonstrated that cultured porcine jejunal cells treated with GLP-2 exhibit increased expression of occludin, claudin-1, and zona occludens-1, which may contribute to enhanced intestinal barrier function. Finally, pre-treatment of weaning pigs with a long-acting GLP-2 analog for 3 d before an intraperitoneal LPS challenge provided multiple intestinal changes that could prevent intestinal injury induced by LPS, including enhancement of the physical barrier function of the gut through increased villus height-to-crypt depth ratio in duodenum, reduced proinflammatory cytokine interleukin 8, interferon-ɣ (IFN-ɣ), and tumor necrosis factor-a (TNF-a) mRNA expression in jejunum, reduced proapoptotic caspase-3 activity in ileum, and increased digestive enzyme lactase and sucrase activities in the proximal small intestine [51,106].…”

Therapeutic effects of different doses of polyethylene glycosylated porcine glucagon-like peptide-2 on ulcerative colitis in male rats

“…This derivative exhibits longer half-life than native pGLP-2 in vitro and can reduce the severity of colonic injury in murine colitis [2]. We demonstrated that 10 nmol/kg/d PEG–pGLP-2 infusion alleviates the severity of intestinal injury in weaning piglets challenged with LPS by reducing the secretion of inflammatory cytokines and increasing the villus height/crypt depth ratio [3]. To provide references for the intestinal injury of weaned pigs by PEG–p[Gly 2 ]GLP-2, the pharmacokinetics of PEG–p[Gly 2 ]GLP-2 was conducted.…”

“…The mono-PEGylated p[Gly 2 ]GLP-2 conjugates were prepared and purified as previously described [3]. Briefly, 1 mg/mL of p[Gly 2 ]GLP-2 in 50 mmol/L Tris-HCl buffer solution was reacted with 4 mole excess of mPEG 5k -SPA at room temperature for 30 min.…”

“…Histology was prepared as previously described [3]. The paraffin-embedded sections were cut at 4 μm thickness and stained with haematoxylin and eosin.…”

“…For the first time, our team designed and purified polyethylene glycosylated (PEGylated) pGLP-2 (PEG-pGLP-2), whose half-life (t 1/2 ) is 16-fold longer than that of pGLP-2 in DPP-IV in vitro [2]. PEG-pGLP-2 infusion could alleviate the severity of intestinal injury in weaning piglets [3, 4]. The t 1/2 of teduglutide, a GLP-2 analogue, which is a candidate for the treatment of short bowel syndrome (SBS) in two phase III clinical studies [5], is 2.99 h in male patient [6].…”