Dataset Information

Glucagon-Like Peptide-2 Modulates Enteric Paneth Cells Immune Response and Alleviates Gut Inflammation During Intravenous Fluid Infusion in Mice With a Central Catheter.

ABSTRACT: Background: Glucagon-like peptide-2 (GLP-2) has protective effects on gastrointestinal functions. Our previous study found that GLP-2 could significantly reduce intestinal permeability and bacterial translocation in total parenteral nutrition (TPN) animal model. However, the effects of GLP-2 on the impairment of the intestinal Paneth cells immune function and gut inflammation during intravenous fluid infusion mainly consisted of nutritional materials is currently scattered. Objective: The current study was aimed to investigate the efficacy of the GLP-2 in alleviating gut inflammation and modulating enteric Paneth cells immune response in parenterally fed mice and its underlying mechanisms. Methods: Thirty-six male ICR mice underwent venous catheterization were divided into 3 groups: Chow, TPN, and TPN+GLP-2 groups. GLP-2 was administered intravenously at 60 μg/day for 5 days. The small intestine tissue and serum samples were collected on the 7th day. Results: Compared with the TPN group, the expression of tight junction proteins occludin and claudin-1 were significantly increased in the TPN+GLP-2 group. In addition, the expression of lysozyme, sPLA2, insulin-like growth factor-1, and epithelial protection and repair genes were improved in the TPN+GLP-2 group. The levels of IL-6 and TNF-α proteins and mRNAs in the ileum tissues were remarkably reduced in the TPN+GLP-2 group, while IL-10 protein and mRNA level were elevated in the TPN+GLP-2 group (all p < 0.05). Moreover, the TPN+GLP-2 group has higher levels of serum endotoxin, D-lactic acid, and MPO than those of the TPN group. Conclusions: GLP-2 alleviated gut inflammation and improved enteric Paneth cells immune responses through intravenous fluid infusion, possibly by improving the functioning of epithelial protection and repair, and reducing mucosal inflammatory responses.

SUBMITTER: Deng G

PROVIDER: S-EPMC8446534 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Glucagon-Like Peptide-2 Modulates Enteric Paneth Cells Immune Response and Alleviates Gut Inflammation During Intravenous Fluid Infusion in Mice With a Central Catheter.

Deng Guifang G Lei Qiucheng Q Gao Xuejin X Zhang Yupeng Y Zheng Huazhen H Bi Jingcheng J Wang Xinying X

Frontiers in nutrition 20210903

<b>Background:</b> Glucagon-like peptide-2 (GLP-2) has protective effects on gastrointestinal functions. Our previous study found that GLP-2 could significantly reduce intestinal permeability and bacterial translocation in total parenteral nutrition (TPN) animal model. However, the effects of GLP-2 on the impairment of the intestinal Paneth cells immune function and gut inflammation during intravenous fluid infusion mainly consisted of nutritional materials is currently scattered. <b>Objective:< ...[more]

PMID: 34540875

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Project description:Type 2 diabetes (T2D) is a pathophysiology that is characterized by insulin resistance, beta- and alpha-cell dysfunction. Mathematical models of various glucose challenge experiments have been developed to quantify the contribution of insulin and beta-cell dysfunction to the pathophysiology of T2D. There is a need for effective extended models that also capture the impact of alpha-cell dysregulation on T2D. In this paper a delay differential equation-based model is developed to describe the coupled glucose-insulin-glucagon dynamics in the isoglycemic intravenous glucose infusion (IIGI) experiment. As the glucose profile in IIGI is tailored to match that of a corresponding oral glucose tolerance test (OGTT), it provides a perfect method for studying hormone responses that are in the normal physiological domain and without the confounding effect of incretins and other gut mediated factors. The model was fit to IIGI data from individuals with and without T2D. Parameters related to glucagon action, suppression, and secretion as well as measures of insulin sensitivity, and glucose stimulated response were determined simultaneously. Significant impairment in glucose dependent glucagon suppression was observed in patients with T2D (duration of T2D: 8 (6-36) months) relative to weight matched control subjects (CS) without diabetes (k1 (mM)-1: 0.16 ± 0.015 (T2D, n = 7); 0.26 ± 0.047 (CS, n = 7)). Insulin action was significantly lower in patients with T2D (a1 (10 pM min)-1: 0.000084 ± 0.0000075 (T2D); 0.00052 ± 0.00015 (CS)) and the Hill coefficient in the equation for glucose dependent insulin response was found to be significantly different in T2D patients relative to CS (h: 1.4 ± 0.15; 1.9 ± 0.14). Trends in parameters with respect to fasting plasma glucose, HbA1c and 2-h glucose values are also presented. Significantly, a negative linear relationship is observed between the glucagon suppression parameter, k1, and the three markers for diabetes and is thus indicative of the role of glucagon in exacerbating the pathophysiology of diabetes (Spearman Rank Correlation: (n = 12; (-0.79, 0.002), (-0.73,.007), (-0.86,.0003)) respectively).

Project description:ImportancePeripherally inserted central catheters (PICCs) are frequently used for peripheral intravenous therapy (IVT) that could be administered through a peripheral midline venous catheter (MVC).ObjectiveTo assess the noninferiority of MVCs compared with PICCs as a reliable vascular access for peripheral IVT and blood draws for IVT that does not require a central VC.Design, setting, and participantsThis randomized clinical trial was conducted in a single tertiary care center from September 2018 to March 2022. Participants were all consecutive adult patients who were referred for PICC and eligible for MVC. Patients likely to require a central VC (those in the critical care unit, those with kidney failure, or those requiring a multilumen VC) were excluded. Analyses were based on the evaluable population.InterventionsParticipants were randomized 1:1 to either MVC or PICC. For the MVC group, a 20-cm-long, 4F (French), single-lumen MVC without a valve was used without fluoroscopic assistance. For the PICC group, a 4F, single-lumen PICC without a valve was positioned under fluoroscopy at the cavoatrial junction.Main outcomes and measuresThe primary outcome was the percentage of patients without VC-related adverse events or dysfunctions requiring medical intervention during follow-up. A noninferiority test was performed to compare the proportion of adverse events or dysfunctions between the MVC and PICC groups. A noninferiority margin was set at 10% and a 5% 1-sided significance level.ResultsOf the 6821 patients referred to the tertiary care center for PICC insertion, 294 (180 males [61.2%]; median [IQR] age, 56.3 [38.2-66.7] years) were randomized to receive MVCs (n = 146) or PICCs (n = 148); 135 and 137 participants, respectively, were included in data analysis after exclusion of those who did not complete follow-up. Ninety of 135 patients (66.7%) in the MVC group and 128 of 137 (93.4%) in the PICC group were without VC-related adverse event or dysfunction. The noninferiority of MVC could not be demonstrated (P > .99 for noninferiority).Conclusions and relevanceIn this randomized clinical trial, MVCs were associated with a significantly higher percentage of patients with VC-related adverse events or dysfunctions and could not be demonstrated as a noninferior alternative to PICCs.Trial registrationClinicalTrials.gov Identifier: NCT03502980.

Dataset Information

Glucagon-Like Peptide-2 Modulates Enteric Paneth Cells Immune Response and Alleviates Gut Inflammation During Intravenous Fluid Infusion in Mice With a Central Catheter.

Publications

Glucagon-Like Peptide-2 Modulates Enteric Paneth Cells Immune Response and Alleviates Gut Inflammation During Intravenous Fluid Infusion in Mice With a Central Catheter.

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