GLP-1 and Intestinal Diseases

Hunt, Jenna; Holst, Jens J.; Jeppesen, Palle Bekker; Kissow, Hannelouise

doi:10.3390/biomedicines9040383

Cited by 36 publications

(29 citation statements)

References 93 publications

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“…This likely results from enhanced nutrient and water absorption in the remnant intestine. The two major mechanisms for such increased absorption are likely prolonged epithelial contact time, largely mediated by the GLP‐1 effect, and increased epithelial mass, largely mediated by the GLP‐2 effect 14,31 . However, experimental evidence that an increased epithelial mass directly translates into increased epithelial function is lacking.…”

Section: Discussionmentioning

confidence: 99%

The dual GLP‐1 and GLP‐2 receptor agonist dapiglutide promotes barrier function in murine short bowel

Reiner

Thiery

Held

et al. 2022

Annals of the New York Academy of Sciences

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Short bowel syndrome can occur after extensive intestinal resection, causing intestinal insufficiency or intestinal failure, which requires long-term parenteral nutrition.Glucagon-like peptide-2 (GLP-2) pharmacotherapy is now clinically used to reduce the disease burden of intestinal failure. However, many patients still cannot be weaned off from parenteral nutrition completely. The novel dual GLP-1 and GLP-2 receptor agonist dapiglutide has previously been shown to be highly effective in a preclinical murine short bowel model. Here, we studied the effects of dapiglutide on intestinal epithelial barrier function. In the jejunum, dapiglutide increased claudin-7 expression and tightened the paracellular tight junction leak pathway. At the same time, dapiglutide promoted paracellular tight junction cation size selectivity in the jejunum. This was paralleled by extension of the cation selective tight junction proteins claudin-2 and claudin-10b and preserved claudin-15 expression and localization along the crypt-villus axis in the jejunum. In the colon, no barrier effects from dapiglutide were observed. In the colon, dapiglutide attenuated the short bowel-associated, compensatorily increased epithelial sodium channel activity, likely secondary, by improved volume status. Future studies are needed to address the intestinal adaptation of the colon.

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Section: Discussionmentioning

confidence: 99%

The dual GLP‐1 and GLP‐2 receptor agonist dapiglutide promotes barrier function in murine short bowel

Reiner

Thiery

Held

et al. 2022

Annals of the New York Academy of Sciences

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“…Previous studies have suggested the use of GLP-1 as a possible treatment of chemotherapy-induced mucositis ( 13 , 18 ). Administration of GLP-1 analogs in mice treated with chemotherapy ameliorated mucositis and accelerated healing of the intestinal injury ( 13 , 14 ).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, increased secretion of GLP-1 is seen after chemotherapy-induced intestinal injury in rodents ( 13 , 14 ), and elevated plasma levels are observed in humans after chemotherapy ( 15 ) and during gut ischemia ( 16 ). Indeed, GLP-1 has intestinotrophic effects sustaining the integrity of intestinal mucosal barrier in animal studies ( 17 , 18 ). Administration of GLP-1 analogs can ameliorate chemotherapy-induced intestinal injury ( 13 ), while ablation of L-cells in mice has led to severe mucositis as well as insufficient intestinal healing after chemotherapy ( 14 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation

et al. 2021

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Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are challenged with severe side effects, which are propagated by mucosal barrier disruption, and the related microbial translocation and systemic inflammation. Glucagon-like peptide-1 (GLP-1), a well-known incretin hormone, possesses anti-inflammatory properties and promotes regeneration of damaged intestinal epithelium in animal studies. We hypothesized that the immense inter-individual variation in the degree of mucosal damage and systemic inflammation, seen after HSCT is influenced by endogenous GLP-1 and could be related to acute post-transplant complications. In this prospective study we measured serial weekly fasting plasma GLP-1, along with C-reactive protein (CRP), and citrulline in 82 pediatric patients during allogeneic HSCT together with a fasting plasma GLP-1 in sex- and age-matched healthy controls. Overall, GLP-1 levels were increased in the patients during the course of HSCT compared with the controls, but tended to decrease post-transplant, most pronounced in patients receiving high-intensity conditioning regimen. The increase in CRP seen in the early post-transplant phase was significantly lower from day +8 to +13 in patients with GLP-1 above the upper quartile (>10 pmol/L) at day 0 (all P ≤ 0.03). Similar findings were seen for peak CRP levels after adjusting for type of conditioning (-47.0%; 95% CI, -8.1 – -69.4%, P = 0.02). Citrulline declined significantly following the transplantation illustrating a decrease in viable enterocytes, most evident in patients receiving high-intensity conditioning regimen. GLP-1 levels at day 0 associated with the recovery rate of citrulline from day 0 to +21 (34 percentage points (pp)/GLP-1 doubling; 95% CI, 10 – 58pp; P = 0. 008) and day 0 to day +90 (48 pp/GLP-1 doubling; 95% CI, 17 – 79pp; P = 0. 004), also after adjustment for type of conditioning. This translated into a reduced risk of acute graft-versus-host disease (aGvHD) in patients with highest day 0 GLP-1 levels (>10 pmol/L) (cause-specific HR: 0.3; 95% CI, 0.2 – 0.9, P = 0.02). In conclusion, this study strongly suggests that GLP-1 influences regeneration of injured epithelial barriers and ameliorates inflammatory responses in the early post-transplant phase.

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“…Агонисты рецепторов ГПП-1 с успехом применяют и при диабетической нефропатии (ДНП) для улучшения сердечно-сосудистого и почечного прогноза [7,12,15]. Имеются данные об их благоприятных эффектах на клинические проявления поражения кишечника, сопут- ствующего СД 2 типа [17]. До настоящего времени нет доказательств наличия у агонистов рецепторов ГПП-1 отчетливых протективных эффектов в отношении диабетической ретинопатии, периферической и вегетативной нейропатии, периферических сосудистых нарушений (диабетическая стопа) [1,15].…”

Section: агониCты рецепторов глюкагоноподобного пептида-1: возможност...unclassified

Glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus

Suprun¹,

Bagriy²,

Mykhailichenko³

et al. 2022

CPT

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An article reviews the use of glucagon-like peptide-1 (GLP-1) receptor agonists for treatment of patients with type 2 diabetes mellitus associated with high cardiovascular risk, chronic heart failure with low left ventricular ejection fraction and diabetic nephropathy. The authors discuss the mechanisms of action of GLP-1 receptor agonists, their main advantages (significant hypoglycemic effect, organoprotection and improved cardiovascular and renal outcomes) and dosedependent side effects.

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GLP-1 and Intestinal Diseases

Cited by 36 publications

References 93 publications

The dual GLP‐1 and GLP‐2 receptor agonist dapiglutide promotes barrier function in murine short bowel

The dual GLP‐1 and GLP‐2 receptor agonist dapiglutide promotes barrier function in murine short bowel

Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation

Glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus

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