• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

肠促胰岛素受体缺失小鼠揭示了胰高血糖素样肽-1而非葡萄糖依赖性促胰岛素多肽在胰腺β细胞适应妊娠中的关键作用。

Incretin receptor null mice reveal key role of GLP-1 but not GIP in pancreatic beta cell adaptation to pregnancy.

作者信息

Moffett R Charlotte, Vasu Srividya, Thorens Bernard, Drucker Daniel J, Flatt Peter R

机构信息

SAAD centre for Pharmacy and Diabetes, University of Ulster, Cromore Road, Coleraine, Northern Ireland.

Centre for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.

出版信息

PLoS One. 2014 Jun 13;9(6):e96863. doi: 10.1371/journal.pone.0096863. eCollection 2014.

DOI:10.1371/journal.pone.0096863
PMID:24927416
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4057070/
Abstract

Islet adaptations to pregnancy were explored in C57BL6/J mice lacking functional receptors for glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). Pregnant wild type mice and GIPRKO mice exhibited marked increases in islet and beta cell area, numbers of medium/large sized islets, with positive effects on Ki67/Tunel ratio favouring beta cell growth and enhanced pancreatic insulin content. Alpha cell area and glucagon content were unchanged but prohormone convertases PC2 and PC1/3 together with significant amounts of GLP-1 and GIP were detected in alpha cells. Knockout of GLP-1R abolished these islet adaptations and paradoxically decreased pancreatic insulin, GLP-1 and GIP. This was associated with abolition of normal pregnancy-induced increases in plasma GIP, L-cell numbers, and intestinal GIP and GLP-1 stores. These data indicate that GLP-1 but not GIP is a key mediator of beta cell mass expansion and related adaptations in pregnancy, triggered in part by generation of intra-islet GLP-1.

摘要

在缺乏胰高血糖素样肽1（GLP-1）和胃抑制性多肽（GIP）功能性受体的C57BL6/J小鼠中，研究了胰岛对妊娠的适应性变化。怀孕的野生型小鼠和GIP受体敲除（GIPRKO）小鼠的胰岛和β细胞面积显著增加，中/大型胰岛数量增多，对Ki67/Tunel比率产生积极影响，有利于β细胞生长，并提高了胰腺胰岛素含量。α细胞面积和胰高血糖素含量没有变化，但在α细胞中检测到激素原转化酶PC2和PC1/3以及大量的GLP-1和GIP。敲除GLP-1受体消除了这些胰岛适应性变化，反而降低了胰腺胰岛素、GLP-1和GIP的含量。这与正常妊娠诱导的血浆GIP增加、L细胞数量以及肠道GIP和GLP-1储存量的增加被消除有关。这些数据表明，GLP-1而非GIP是妊娠期间β细胞质量扩张和相关适应性变化的关键介质，部分是由胰岛内GLP-1的产生引发的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/d33336b15129/pone.0096863.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/2ea3b52f8423/pone.0096863.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/56dba082756f/pone.0096863.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/97f71bfa748b/pone.0096863.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/e0a731f5b770/pone.0096863.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/2b54dba8a7c2/pone.0096863.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/1c2d293c5f76/pone.0096863.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/42a53bb6a7e9/pone.0096863.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/d33336b15129/pone.0096863.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/2ea3b52f8423/pone.0096863.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/56dba082756f/pone.0096863.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/97f71bfa748b/pone.0096863.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/e0a731f5b770/pone.0096863.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/2b54dba8a7c2/pone.0096863.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/1c2d293c5f76/pone.0096863.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/42a53bb6a7e9/pone.0096863.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/4057070/d33336b15129/pone.0096863.g008.jpg

相似文献

1
Incretin receptor null mice reveal key role of GLP-1 but not GIP in pancreatic beta cell adaptation to pregnancy.肠促胰岛素受体缺失小鼠揭示了胰高血糖素样肽-1而非葡萄糖依赖性促胰岛素多肽在胰腺β细胞适应妊娠中的关键作用。
PLoS One. 2014 Jun 13;9(6):e96863. doi: 10.1371/journal.pone.0096863. eCollection 2014.
2
Functional GIP receptors play a major role in islet compensatory response to high fat feeding in mice.功能性胃抑制多肽（GIP）受体在小鼠胰岛对高脂喂养的代偿反应中起主要作用。
Biochim Biophys Acta. 2015 Jun;1850(6):1206-14. doi: 10.1016/j.bbagen.2015.02.006. Epub 2015 Feb 14.
3
Role of endogenous GLP-1 and GIP in beta cell compensatory responses to insulin resistance and cellular stress.内源性胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性促胰岛素多肽（GIP）在β细胞对胰岛素抵抗和细胞应激的代偿反应中的作用。
PLoS One. 2014 Jun 26;9(6):e101005. doi: 10.1371/journal.pone.0101005. eCollection 2014.
4
Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function.2型糖尿病中TCF7L2蛋白水平降低与GIP和GLP-1受体下调及β细胞功能受损相关。
Hum Mol Genet. 2009 Jul 1;18(13):2388-99. doi: 10.1093/hmg/ddp178. Epub 2009 Apr 21.
5
Differential importance of glucose-dependent insulinotropic polypeptide vs glucagon-like peptide 1 receptor signaling for beta cell survival in mice.葡萄糖依赖性促胰岛素多肽与胰高血糖素样肽1受体信号传导对小鼠β细胞存活的不同重要性
Gastroenterology. 2009 Dec;137(6):2146-57. doi: 10.1053/j.gastro.2009.09.004. Epub 2009 Sep 17.
6
Glucose-dependent insulinotropic polypeptide is expressed in pancreatic islet alpha-cells and promotes insulin secretion.葡萄糖依赖性胰岛素促泌多肽在胰岛α细胞中表达，并促进胰岛素分泌。
Gastroenterology. 2010 May;138(5):1966-75. doi: 10.1053/j.gastro.2010.01.049. Epub 2010 Feb 4.
7
Expression and functional activity of glucagon, glucagon-like peptide I, and glucose-dependent insulinotropic peptide receptors in rat pancreatic islet cells.胰高血糖素、胰高血糖素样肽I及葡萄糖依赖性促胰岛素多肽受体在大鼠胰岛细胞中的表达及功能活性
Diabetes. 1996 Feb;45(2):257-61. doi: 10.2337/diab.45.2.257.
8
Enhanced glucose-dependent insulinotropic polypeptide secretion and insulinotropic action in glucagon-like peptide 1 receptor -/- mice.胰高血糖素样肽1受体基因敲除小鼠中葡萄糖依赖性促胰岛素多肽分泌增强及促胰岛素作用增强
Diabetes. 1998 Jul;47(7):1046-52. doi: 10.2337/diabetes.47.7.1046.
9
GIP and GLP-1 as incretin hormones: lessons from single and double incretin receptor knockout mice.作为肠促胰岛素激素的葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽-1（GLP-1）：来自单和双肠促胰岛素受体敲除小鼠的经验教训。
Regul Pept. 2005 Jun 15;128(2):125-34. doi: 10.1016/j.regpep.2004.07.019.
10
Glucose-dependent insulinotropic polypeptide receptor null mice exhibit compensatory changes in the enteroinsular axis.葡萄糖依赖性促胰岛素多肽受体缺失小鼠在肠胰岛轴中表现出代偿性变化。
Am J Physiol Endocrinol Metab. 2003 May;284(5):E931-9. doi: 10.1152/ajpendo.00270.2002. Epub 2003 Jan 21.

引用本文的文献

1
Glucose-dependent insulinotropic polypeptide (GIP).葡萄糖依赖性促胰岛素多肽（GIP）。
Mol Metab. 2025 May;95:102118. doi: 10.1016/j.molmet.2025.102118. Epub 2025 Feb 28.
2
Cafeteria diet compromises natural adaptations of islet cell transdifferentiation and turnover in pregnancy.自助餐式饮食会损害孕期胰岛细胞转分化和更新的自然适应性。
Diabet Med. 2025 Jan;42(1):e15434. doi: 10.1111/dme.15434. Epub 2024 Sep 10.
3
Genetics of glucose homeostasis in pregnancy and postpartum.妊娠期及产后血糖稳态的遗传学。

本文引用的文献

1
Cardiovascular benefits of incretins.肠促胰岛素的心血管益处。
BMJ. 2013 Jul 10;347:f4382. doi: 10.1136/bmj.f4382.
2
Do current incretin mimetics exploit the full therapeutic potential inherent in GLP-1 receptor stimulation?目前的肠促胰岛素类似物是否充分利用了 GLP-1 受体刺激所固有的全部治疗潜力？
Diabetologia. 2013 Sep;56(9):1878-83. doi: 10.1007/s00125-013-2953-6. Epub 2013 Jun 8.
3
Pharmacology, physiology, and mechanisms of incretin hormone action.肠降血糖素激素作用的药理学、生理学和机制。
Diabetologia. 2024 Dec;67(12):2726-2739. doi: 10.1007/s00125-024-06256-8. Epub 2024 Aug 24.
4
Maternal GLP-1 receptor activation inhibits fetal growth.母体 GLP-1 受体的激活会抑制胎儿生长。
Am J Physiol Endocrinol Metab. 2024 Mar 1;326(3):E268-E276. doi: 10.1152/ajpendo.00361.2023. Epub 2024 Jan 10.
5
Pregnancy glucagon-like peptide 1 predicts insulin but not glucose concentrations.妊娠胰高血糖素样肽 1 可预测胰岛素而非血糖浓度。
Acta Diabetol. 2023 Dec;60(12):1635-1642. doi: 10.1007/s00592-023-02142-8. Epub 2023 Jul 13.
6
Circadian hormone secretion of enteroendocrine cells: implication on pregnancy status.肠内分泌细胞的昼夜激素分泌：对妊娠状态的影响。
Front Endocrinol (Lausanne). 2023 May 10;14:1106382. doi: 10.3389/fendo.2023.1106382. eCollection 2023.
7
The human α cell in health and disease.人类α细胞在健康和疾病中的作用。
J Endocrinol. 2023 Jun 19;258(1). doi: 10.1530/JOE-22-0298. Print 2023 Jul 1.
8
Evidence for Involvement of GIP and GLP-1 Receptors and the Gut-Gonadal Axis in Regulating Female Reproductive Function in Mice.证据表明，GIP 和 GLP-1 受体以及肠道-性腺轴参与调节小鼠的雌性生殖功能。
Biomolecules. 2022 Nov 23;12(12):1736. doi: 10.3390/biom12121736.
9
Pregnancy induces pancreatic insulin secretion in women with long-standing type 1 diabetes.妊娠可诱导长期 1 型糖尿病女性的胰腺胰岛素分泌。
BMJ Open Diabetes Res Care. 2022 Nov;10(6). doi: 10.1136/bmjdrc-2022-002948.
10
Alpha-cell paracrine signaling in the regulation of beta-cell insulin secretion.α 细胞旁分泌信号在调节 β 细胞胰岛素分泌中的作用。
Front Endocrinol (Lausanne). 2022 Jul 26;13:934775. doi: 10.3389/fendo.2022.934775. eCollection 2022.
Cell Metab. 2013 Jun 4;17(6):819-837. doi: 10.1016/j.cmet.2013.04.008. Epub 2013 May 16.
4
No evidence for β cell neogenesis in murine adult pancreas.在成年鼠胰腺中没有β细胞新生的证据。
J Clin Invest. 2013 May;123(5):2207-17. doi: 10.1172/JCI66323. Epub 2013 Apr 24.
5
Ectopic expression of GIP in pancreatic β-cells maintains enhanced insulin secretion in mice with complete absence of proglucagon-derived peptides.胰岛β细胞异位表达 GIP 可维持缺乏胰高血糖素原衍生肽的小鼠增强的胰岛素分泌。
Diabetes. 2013 Feb;62(2):510-8. doi: 10.2337/db12-0294. Epub 2012 Oct 25.
6
Chemical cholecystokinin receptor activation protects against obesity-diabetes in high fat fed mice and has sustainable beneficial effects in genetic ob/ob mice.化学胆囊收缩素受体激活可预防高脂喂养小鼠的肥胖-糖尿病，并对遗传肥胖（ob/ob）小鼠具有可持续的有益作用。
Biochem Pharmacol. 2013 Jan 1;85(1):81-91. doi: 10.1016/j.bcp.2012.10.008. Epub 2012 Oct 17.
7
MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity.微小 RNA 有助于妊娠和肥胖期间胰岛 β 细胞的代偿性扩张。
J Clin Invest. 2012 Oct;122(10):3541-51. doi: 10.1172/JCI64151. Epub 2012 Sep 10.
8
A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets.人胰岛内的局部胰高血糖素样肽 1 (GLP-1) 系统。
Diabetologia. 2012 Dec;55(12):3262-72. doi: 10.1007/s00125-012-2716-9. Epub 2012 Sep 11.
9
Fertility and pregnancy-associated ß-cell proliferation in mice deficient in proglucagon-derived peptides.小鼠前胰高血糖素衍生肽缺失导致的生育和妊娠相关的β细胞增殖。
PLoS One. 2012;7(8):e43745. doi: 10.1371/journal.pone.0043745. Epub 2012 Aug 23.
10
Regulation of mouse intestinal L cell progenitors proliferation by the glucagon family of peptides.胰高血糖素家族肽对小鼠肠 L 细胞前体细胞增殖的调控。
Endocrinology. 2012 Jul;153(7):3076-88. doi: 10.1210/en.2012-1120. Epub 2012 May 8.