Email Alerts
RSS
Volume 40 Issue 7
Jul.  2024
Turn off MathJax
Article Contents
Abstract
References
Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2024  >  40(7): 625-633
Zhang C,Peng Y,Luo XQ,et al.Epidemiological investigation and analysis of etiological characteristics of infection on 3 067 hospitalized pediatric patients with burns[J].Chin J Burns,2021,37(0):538-545.DOI: 10.3760/cma.j.cn501120-20210201-00044.
Citation: Liu XZ,Li DW,Jiang M,et al.Changes in entero-insular axis function and its role in mice with severe burns[J].Chin J Burns Wounds,2024,40(7):625-633.DOI: 10.3760/cma.j.cn501225-20240520-00189.
shu

Changes in entero-insular axis function and its role in mice with severe burns

doi: 10.3760/cma.j.cn501225-20240520-00189

  • Senior Department of Burns and Plastic Surgery, the Fourth Medical Center of PLA General Hospital, Beijing 100048, China

Funds:

General Program of National Natural Science Foundation of China 82072169, 82272279

Youth Science Fund Project of National Natural Science Foundation of China 82302799

PLA General Hospital Youth Independent Innovation Science Fund Project 22QNFC011

More Information
    Abstract
  •   Objective  To explore the changes in entero-insular axis function and its role in mice with severe burns.  Methods  This study was an experimental study. Ninety C57BL/6J male mice aged 8-10 weeks were divided into sham injury group and burn group (with 45 mice in each group) according to the random number table. A full-thickness scald (hereinafter referred to as burn) wound of 30% of the total body surface area was created on the back of mice in burn group, and the mice in sham injury group were simulated to cause a sham injury. Twenty-four hours after injury, the fasting blood glucose was measured (n=12), followed by intraperitoneal glucose tolerance test and oral glucose tolerance test; the curve of blood glucose concentration changes over time was plotted, and the area under the curve was calculated (n=6); the blood was taken from the heart before intraperitoneal injection or gavage of glucose solution and at 30, 60, and 120 minutes after intraperitoneal injection or gavage of glucose solution for measuring the plasma insulin and glucagon like peptide-1 (GLP-1) levels using enzyme-linked immunosorbent assay (ELISA), with a sample number of 3; the ileal tissue was taken from 3 mice in each group for detecting the GLP-1 expression and apoptosis levels of intestinal L cells by immunofluorescence staining and TdT-mediated dUTP nick-end labeling staining; the pancreatic islets were collected from 6 mice in each group for glucose-stimulated insulin secretion experiments. After incubation with low glucose (2.8 mmol/L glucose) and high glucose (16.7 mmol/L glucose), the supernatant was taken and the insulin level was detected using ELISA. Thirty-six C57BL/6J male mice aged 8-10 weeks were divided into sham injury group, burn group, and burn+exendin-4 (Ex-4) group (with 12 mice in each group) according to the random number table. The mice in sham injury group and burn group were subjected to the same corresponding treatment as before. The mice in burn+Ex-4 group were injured in the same way as the burn group mice followed by treatment with GLP-1 receptor agonist Ex-4. Twenty-four hours after injury, mouse pancreatic islets were collected, the protein expressions of heavy-chain binding protein (BIP), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), eukaryotic translation initiation factor 2α (eIF2α), phosphorylated eIF2α (p-eIF2α), and CCAAT/enhancer-binding protein homologous protein (CHOP) were detected using Western blotting, and the p-PERK/PERK and p-eIF2α/eIF2α ratios were calculated (n=3), the apoptosis rate of pancreatic islet cells was detected using flow cytometry (n=3), the glucose stimulated insulin secretion experiment was conducted as before to detect insulin levels in the supernatant (n=6).  Results  Twenty-four hours after injury, the fasting blood glucose of mice in burn group was (7.3±1.0) mmol/L, which was significantly higher than (5.1±0.6) mmol/L in sham injury group (t=6.36, P<0.05). Twenty-four hours after injury, in the intraperitoneal glucose tolerance test and oral glucose tolerance test, the areas under the curve of blood glucose concentration changes over time of mice in burn group were significantly larger than those in sham injury group (with t values of 4.32 and 6.03, respectively, P<0.05); compared with those in sham injury group, the plasma insulin levels of mice before intraperitoneal injection of glucose solution and the plasma GLP-1 levels of mice before intraperitoneal injection or gavage of glucose solution in burn group were significantly decreased (P<0.05), and the plasma levels of insulin of mice at 30, 60, and 120 minutes after intraperitoneal injection or gavage of glucose solution, as well as the plasma levels of GLP-1 of mice at 30 and 60 minutes after gavage of glucose solution were significantly decreased in burn group (P<0.05). Twenty-four hours after injury, compared with those in sham injury group, the GLP-1 expression level of intestinal L cells of mice in burn group was significantly decreased (t=7.74, P<0.05), and the apoptosis level was significantly increased (t=14.28, P<0.05). Twenty-four hours after injury, the insulin level in the supernatant of mice pancreatic islet incubated with high glucose in burn group was (8.5±0.4) ng/mg, which was significantly lower than (15.7±0.3) ng/mg in sham injury group (t=18.68, P<0.05). Twenty-four hours after injury, compared with those in sham injury group, the protein expression levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, and CHOP in the pancreatic islets of mice in burn group were significantly increased (P<0.05); compared with those in burn group, the protein expression levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, and CHOP in the pancreatic islets of mice in burn+Ex-4 group were significantly decreased (P<0.05). Twenty-four hours after injury, the apoptosis rate of pancreatic islet cells of mice in burn group was (32.0±3.0)%, which was significantly higher than (10.3±2.5)% in sham injury group (P<0.05); the apoptosis rate of pancreatic islet cells of mice in burn+Ex-4 group was (20.0±3.6)%, which was significantly lower than that in burn group (P<0.05). Twenty-four hours after injury, the insulin level in the supernatant of mice pancreatic islet incubated with high glucose in burn group was significantly lower than that in sham injury group (P<0.05), while the insulin level in the supernatant of mice pancreatic islet incubated with high glucose in burn+Ex-4 group was significantly higher than that in burn group (P<0.05).  Conclusions  After severe burns, the mice display dysfunction of the entero-insular axis, increased apoptosis of intestinal L cells, decreased synthesis and secretion of GLP-1, endoplasmic reticulum stress and increased apoptosis in pancreatic islet cells and a decrease in glucose-stimulated insulin secretion. The GLP-1 receptor agonist Ex-4 can protect the function of pancreatic islet cells of mice with severe burns, reducing the apoptosis level of pancreatic islet cells and promoting insulin secretion possibly via the alleviation of endoplasmic reticulum stress.

     

    • FullText(HTML)
    • References(30)
  • [1]
    Pérez-AranaGM,Díaz-GómezA,Camacho-RamírezA,et al.Dual effect of RYGB on the entero-insular axis: how GLP-1 is enhanced by surgical duodenal exclusion[J].Ann Anat,2023,249:152094.DOI: 10.1016/j.aanat.2023.152094.
    [2]
    PorterC,TompkinsRG,FinnertyCC,et al.The metabolic stress response to burn trauma: current understanding and therapies[J].Lancet,2016,388(10052):1417-1426.DOI: 10.1016/S0140-6736(16)31469-6.
    [3]
    LiZ,LiuX,ZhangK,et al.Role and mechanism of endoplasmic reticulum stress in mice pancreatic islet dysfunction after severe burns[J].J Burn Care Res,2023,44(5):1231-1240.DOI: 10.1093/jbcr/irad029.
    [4]
    LiuX,LiuZ,LiD,et al.Mitochondria play a key role in oxidative stress-induced pancreatic islet dysfunction after severe burns[J].J Trauma Acute Care Surg,2022,92(6):1012-1019.DOI: 10.1097/TA.0000000000003490.
    [5]
    张博涵,申传安,孙鹏超,等.严重烫伤大鼠早期胰岛素分泌功能变化及信号转导机制[J].中华烧伤杂志,2020,36(4):280-287.DOI: 10.3760/cma.j.cn501120-20190702-00289.
    [6]
    ZhangB,SunP,ShenC,et al.Role and mechanism of PI3K/AKT/FoxO1/PDX-1 signaling pathway in functional changes of pancreatic islets in rats after severe burns[J].Life Sci,2020,258:118145.DOI: 10.1016/j.lfs.2020.118145.
    [7]
    UngerRH,EisentrautAM.Entero-insular axis[J].Arch Intern Med,1969,123(3):261-266.
    [8]
    Santos-HernándezM,ReimannF,GribbleFM.Cellular mechanisms of incretin hormone secretion[J].J Mol Endocrinol,2024,72(4):e230112.DOI: 10.1530/JME-23-0112.
    [9]
    HolstJJ.The incretin system in healthy humans: the role of GIP and GLP-1[J].Metabolism,2019,96:46-55.DOI: 10.1016/j.metabol.2019.04.014.
    [10]
    ShenCA,FaganS,FischmanAJ,et al.Effects of glucagon-like peptide 1 on glycemia control and its metabolic consequence after severe thermal injury--studies in an animal model[J].Surgery,2011,149(5):635-644.DOI: 10.1016/j.surg.2010.11.017.
    [11]
    LiuX,XieX,LiD,et al.Sirt3-dependent regulation of mitochondrial oxidative stress and apoptosis contributes to the dysfunction of pancreatic islets after severe burns[J].Free Radic Biol Med,2023,198:59-67.DOI: 10.1016/j.freeradbiomed.2023.01.027.
    [12]
    TuggleDW,KuhnMA,JonesSK,et al.Hyperglycemia and infections in pediatric trauma patients[J].Am Surg,2008,74(3):195-198.DOI: 10.1177/000313480807400302.
    [13]
    GoreDC,ChinkesD,HeggersJ,et al.Association of hyperglycemia with increased mortality after severe burn injury[J].J Trauma,2001,51(3):540-544.DOI: 10.1097/00005373-200109000-00021.
    [14]
    PidcokeHF,WanekSM,RohlederLS,et al.Glucose variability is associated with high mortality after severe burn[J].J Trauma,2009,67(5):990-995.DOI: 10.1097/TA.0b013e3181baef4b.
    [15]
    LiS,LiD,LiY,et al.Development and validation of a nomogram for pneumonia risk in burn patients with inhalation injury: a multicenter retrospective cohort study[J].Int J Surg,2024,110(5):2902-2909.DOI: 10.1097/JS9.0000000000001190.
    [16]
    van den BergheG,WoutersP,WeekersF,et al.Intensive insulin therapy in critically ill patients[J].N Engl J Med,2001,345(19):1359-1367.DOI: 10.1056/NEJMoa011300.
    [17]
    CampbellJE,DruckerDJ.Pharmacology, physiology, and mechanisms of incretin hormone action[J].Cell Metab,2013,17(6):819-837.DOI: 10.1016/j.cmet.2013.04.008.
    [18]
    D'AlessioD.Is GLP-1 a hormone: whether and when?[J].J Diabetes Investig,2016,7Suppl 1(Suppl 1):S50-55.DOI: 10.1111/jdi.12466.
    [19]
    NauckMA,HombergerE,SiegelEG,et al.Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses[J].J Clin Endocrinol Metab,1986,63(2):492-498.DOI: 10.1210/jcem-63-2-492.
    [20]
    HolstJJ,GasbjergLS,RosenkildeMM.The role of incretins on insulin function and glucose homeostasis[J].Endocrinology,2021,162(7):bqab065.DOI: 10.1210/endocr/bqab065.
    [21]
    SodumN,MattilaO,SharmaR,et al.Nutrient combinations sensed by L-cell receptors potentiate GLP-1 secretion[J].Int J Mol Sci,2024,25(2):1087.DOI: 10.3390/ijms25021087.
    [22]
    MüllerTD,FinanB,BloomSR,et al.Glucagon-like peptide 1 (GLP-1)[J].Mol Metab,2019,30:72-130.DOI: 10.1016/j.molmet.2019.09.010.
    [23]
    YingW,FuW,LeeYS,et al.The role of macrophages in obesity-associated islet inflammation and β-cell abnormalities[J].Nat Rev Endocrinol,2020,16(2):81-90.DOI: 10.1038/s41574-019-0286-3.
    [24]
    LiuYT,HeT,LiHQ,et al.Liraglutide improves pancreatic islet β cell apoptosis in rats with type 2 diabetes mellitus by inhibiting the IKKε/NF-κB pathway[J].Eur Rev Med Pharmacol Sci,2021,25(14):4818-4828.DOI: 10.26355/eurrev_202107_26395.
    [25]
    WeiR,CuiX,FengJ,et al.Dapagliflozin promotes beta cell regeneration by inducing pancreatic endocrine cell phenotype conversion in type 2 diabetic mice[J].Metabolism,2020,111:154324.DOI: 10.1016/j.metabol.2020.154324.
    [26]
    NauckMA,QuastDR,WefersJ,et al.GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art[J].Mol Metab,2021,46:101102.DOI: 10.1016/j.molmet.2020.101102.
    [27]
    ReedJ,BainS,KanamarlapudiV.A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives[J].Diabetes Metab Syndr Obes,2021,14:3567-3602.DOI: 10.2147/DMSO.S319895.
    [28]
    LiD,ShangY,ShenC,et al.Effects of Exendin-4 on pancreatic islets function in treating hyperglycemia post severe scald injury in rats[J].J Trauma Acute Care Surg,2018,85(6):1072-1080.DOI: 10.1097/TA.0000000000002066.
    [29]
    LiuM,WeissMA,ArunagiriA,et al.Biosynthesis, structure, and folding of the insulin precursor protein[J].Diabetes Obes Metab,2018,20Suppl 2(Suppl 2):S28-50.DOI: 10.1111/dom.13378.
    [30]
    KwonDY,KimYS,AhnIS,et al.Exendin-4 potentiates insulinotropic action partly via increasing beta-cell proliferation and neogenesis and decreasing apoptosis in association with the attenuation of endoplasmic reticulum stress in islets of diabetic rats[J].J Pharmacol Sci,2009,111(4):361-371.DOI: 10.1254/jphs.09178fp.
    • Relative Articles

  • Relative Articles

    [1]Fan Fuxiao, Li Pengtao, Xia Zhengguo, Xie Chaoqiong, Xu Jiegou, Xu Qinglian. Effects and molecular mechanism of exogenous L-carnitine on excessive endoplasmic reticulum stress-mediated hepatic pyroptosis in severely scald rats[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2022, 38(7): 667-676. doi: 10.3760/cma.j.cn501225-20220120-00010
    [2]Zhang Bohan, Shen Chuan′an, Sun Pengchao, Zheng Bo, Li Dawei, Liu Zhaoxing, Xu Shengbo, Sun Jiachen, Zhang Wen. Changes of insulin secretion and its signal transduction mechanism at early stage of severe scald in rats[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2020, 36(4): 280-287. doi: 10.3760/cma.j.cn501120-20190702-00289
    [3]Chu Wanli, Chai Jiake, Wang Xiaoteng, Han Shaofang, Liu Lingying. Effects of insulin therapy on skeletal muscle wasting in severely scalded rats and its related mechanism[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2019, 35(5): 333-340. doi: 10.3760/cma.j.issn.1009-2587.2019.05.003
    [4]Zhao Dongxu, Ma Li, Shen Chuan′an, Li Dawei, Shang Yuru, Yin Kai, Cheng Wenfeng, Wang Xin, Liu Zhaoxing. Influences of exendin-4 on the secretion function of islet beta cells from rats in the early stage of severe scald[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2016, 32(12): 752-758. doi: 10.3760/cma.j.issn.1009-2587.2016.12.011
    [7]SHE Tao, HU Da-hai, ZHANG Yan-gang, HU Xiao-long, ZHANG Wan-fu, LIU Jia-qi, CAI Wei-xia, ZHANG Zhan-feng. Biological effects of paracrine from insulin stimulated adipose-derived stem cells （ADSC） on human vascular endothelial cells[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2011, 27(1): 32-36. doi: 10.3760/cma.j.issn.1009-2587.2011.01.009
    [8]ZHANG Zhao-xin, LIU Xiao-long, LU Lei, ZHANG Liang, JI Dong-liang, LIU Li-hua. Effect of insulin by local injection on the level of systemic blood glucose and granulation tissue formation of wound in patients with diabetic foot ulcer[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2011, 27(6): 451-455. doi: 10.3760/cma.j.issn.1009-2587.2011.06.014
    [9]MA Li, CHAI Jia-ke, SHFN Chuan-an, CHI Yun-fei, FENG Rui, DENG Hu-ping. Modulatory effect of insulin on scalded rat serum-induced apoptosis of skeletal myoblast[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2011, 27(5): 353-357. doi: 10.3760/cma.j.issn.1009-2587.2011.05.008
    [10]SHEN Chuan-an, CHAI Jia-ke, MA Li, HAI Heng-lin, ZHANG Lin. Regulatory effect of glucagon-like peptide-1 on cell proliferation of skeletal myoblast strain L6 and its possible signal mechanism[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2011, 27(5): 332-336. doi: 10.3760/cma.j.issn.1009-2587.2011.05.003
    [11]ZHANG Wan-fu, HU Da-hai, XU Cheng-feng, Lv Gen-fa, DONG Mao-long, ZHAO Zhou-ting, ZHU Xiong-xiang. Inhibitory effect of insulin on nuclear factor-kappa B nuclear translocation of vascular endothelial cells induced by burn serum[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2010, 26(3): 175-179. doi: 10.3760/cma.j.issn.1009-2587.2010.03.003
    [12]DUAN Hong-jie, CHAI Jia-ke, SHENG Zhi-yong, YAO Yong-ming, YIN Hui-nan, SHEN Chuan-an, WU Yan-qiu, HU Quan, LIANG Li-ming. Effect of intensive insulin therapy on apoptosis-related ligands in serum in rats with severe scald[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2009, 25(1): 42-45. doi: 10.3760/cma.j.issn.1009-2587.2009.01.016
    [13]LV Gen-fa, CHEN Bi, ZHANG Wan-fu, DONG Mao-long, ZHU Xiong-xiang, HU Da-hai. The anti-apoptosis effect of intensive insulin treatment on cardiac myocytes in severe scald rats[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2008, 24(3): 179-182.
    [14]LV Gen-fa, CHEN Bi, ZHANG Wan-fu, WANG Yun-chuan, CAI Wei-xia, TANG Chao-wu, ZHU Xiong-xiang, DONG Mao-long, HU Da-hai. The protective effect of intensive insulin treatment on the myocardium in severely scalded rats[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2007, 23(3): 168-171.
    [15]WANG Yun-chuan, JIA Chi-yu, ZHANG Wan-fu, LV Gen-fa, DONG Mao-long, TANG Chao-wu, HU Da-hai. Protective effect of insulin on oxygen-radical induced hepatic injury in severely scalded rats[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2007, 23(6): 428-431.
    [16]GUO Guang-hua, CAI Chen, FAN Jun, ZHANG Hong-yan, LI Guo-hui, . The protective effect of early insulin treatment on vascular endothelial cells in severely scalded rats[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2007, 23(4): 261-264.
    [17]CHEN Jian-fang, YAO Zhong-xiang. Expression of insulin in the brain tissue of rats after scald[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2006, 22(6): 434-436.
    [19]LIU Yan, ZHANG Xiong, ZHANG Zhi, XU Wei-shi. The influence of topical application of insulin on the formation of basement membrane in scalded rats[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2005, 21(6): 445-447.
    [20]LIU Yan, ZHANG Xiong, ZHANG Zhi, FANG Pei-yao, XU Wei-shi. Effects of topical application of insulin on the wound healing in scalded rats[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2004, 20(2): 98-101.
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(4)  / Tables(4)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (993) PDF downloads(17) Cited by()
    Proportional views
    Related

    Copyright © Chinese Journal of Burns京ICP备07035254号-14

    E-mail：shaoshangzazhi@163.com

    Website：https://zhsszz.xml-journal.net/

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return