Efficacy of glucagon-like peptide-1 and estrogen dual agonist in pancreatic islets protection and pre-clinical models of insulin-deficient diabetes.
Efficacy of glucagon-like peptide-1 and estrogen dual agonist in pancreatic islets protection and pre-clinical models of insulin-deficient diabetes.
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DOI：
10.1016/j.xcrm.2022.100598
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发表时间：
2022-04-19
影响因子：
14.3
通讯作者：
Mauvais-Jarvis, Franck
中科院分区：
文献类型：
--
作者：
Fuselier, Taylor;de Sa, Paula Mota;Qadir, M. M. Fahd;Xu, Beibei;Allard, Camille;Meyers, Mathew M.;Tiano, Joseph P.;Yang, Bin S.;Gelfanov, Vasily;Lindsey, Sarah H.;Dimarchi, Richard D.;Mauvais-Jarvis, Franck
我们研究了胰高血糖素样肽-1（GLP-1）和雌激素双重激动剂（GLP 1-E2）在胰岛保护中的功效。与GLP-1单激动剂相比，GLP 1-E2对小鼠多次低剂量链脲佐菌素（MLD-STZ-糖尿病）和秋田突变诱导的胰岛素缺乏型糖尿病提供了上级保护。GLP 1-E2不能预防雌激素受体-α（ERα）缺陷小鼠的MLD-STZ糖尿病，并且在GLP-1受体（GLP-1 R）拮抗作用后也不能预防秋田小鼠的糖尿病，这表明GLP 1-E2抗糖尿病作用需要GLP-1 R和ERα。在MIN 6 β细胞模型中，GLP 1-E2在网格蛋白依赖性、GLP-1 R介导的内化和溶酶体酸化后激活雌激素作用。在培养的人胰岛中，蛋白质组学生物信息学分析表明，GLP 1-E2放大了由单激动剂激活的抗凋亡途径。然而，在培养的小鼠胰岛中，GLP 1-E2提供了类似于单激动剂的抗凋亡保护。因此，GLP 1-E2在培养的胰岛中促进GLP-1和E2抗凋亡信号，但在体内，GLP 1-E2在表达GLP-1 R的非胰岛细胞中的额外作用有助于预防糖尿病。GLP 1-E2增强GLP-1介导的对小鼠胰岛素缺乏型糖尿病的保护作用GLP 1-E2在GLP-1 R内化和溶酶体酸化后激活ERα GLP 1-E2增强GLP-1在人β细胞中激活的抗凋亡途径GLP 1-E2降糖作用涉及胰岛外的GLP-1 R表达细胞Fuselier et al.报告称，与GLP-1和E2单激动剂相比，胰高血糖素样肽-1和雌激素双重激动剂（GLP 1-E2）通过靶向递送至β细胞和共表达GLP-1 R和ERα的非胰岛细胞中的GLP-1受体（GLP-1 R）和雌激素受体-α（ERα），在小鼠中提供了上级胰岛素缺乏型糖尿病保护。
We study the efficacy of a glucagon-like peptide-1 (GLP-1) and estrogen dual agonist (GLP1-E2) in pancreatic islet protection. GLP1-E2 provides superior protection from insulin-deficient diabetes induced by multiple low-dose streptozotocin (MLD-STZ-diabetes) and by the Akita mutation in mice than a GLP-1 monoagonist. GLP1-E2 does not protect from MLD-STZ-diabetes in estrogen receptor-α (ERα)-deficient mice and fails to prevent diabetes in Akita mice following GLP-1 receptor (GLP-1R) antagonism, demonstrating the requirement of GLP-1R and ERα for GLP1-E2 antidiabetic actions. In the MIN6 β cell model, GLP1-E2 activates estrogen action following clathrin-dependent, GLP-1R-mediated internalization and lysosomal acidification. In cultured human islet, proteomic bioinformatic analysis reveals that GLP1-E2 amplifies the antiapoptotic pathways activated by monoagonists. However, in cultured mouse islets, GLP1-E2 provides antiapoptotic protection similar to monoagonists. Thus, GLP1-E2 promotes GLP-1 and E2 antiapoptotic signals in cultured islets, but in vivo, additional GLP1-E2 actions in non-islet cells expressing GLP-1R are instrumental to prevent diabetes. GLP1-E2 enhances GLP-1-mediated protection of insulin-deficient diabetes in mice GLP1-E2 activates ERα following GLP-1R internalization and lysosomal acidification GLP1-E2 amplifies antiapoptotic pathways activated by GLP-1 in human β cells GLP1-E2 antidiabetic actions involve GLP-1R-expressing cells outside the islets Fuselier et al. report that a glucagon-like peptide-1 and estrogen dual agonist (GLP1-E2) provides superior protection from insulin-deficient diabetes in mice compared to GLP-1 and E2 monoagonists, via targeted delivery to GLP-1 receptor (GLP-1R) and estrogen receptor-α (ERα) in β cells, and non-islet cells co-expressing GLP-1R and ERα.
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雌激素受体ERα调节胰腺胰岛素含量。
影响因子：
3.7
作者：
Alonso-Magdalena, Paloma;Ropero, Ana B.;Carrera, M. Pilar;Cederroth, Christopher R.;Baquie, Mathurin;Gauthier, Benoit R.;Nef, Serge;Stefani, Enrico;Nadal, Angel
通讯作者：
Nadal, Angel
影响因子：
16.6
作者：
Jones B;Buenaventura T;Kanda N;Chabosseau P;Owen BM;Scott R;Goldin R;Angkathunyakul N;Corrêa IR Jr;Bosco D;Johnson PR;Piemonti L;Marchetti P;Shapiro AMJ;Cochran BJ;Hanyaloglu AC;Inoue A;Tan T;Rutter GA;Tomas A;Bloom SR
通讯作者：
Bloom SR
影响因子：
7.7
作者：
Liu S;Le May C;Wong WP;Ward RD;Clegg DJ;Marcelli M;Korach KS;Mauvais-Jarvis F
通讯作者：
Mauvais-Jarvis F
DOI：
10.1073/pnas.0602956103
发表时间：
2006-06-13
影响因子：
11.1
作者：
Le May, Cedric;Chu, Khoi;Mauvais-Jarvis, Franck
通讯作者：
Mauvais-Jarvis, Franck
影响因子：
15.9
作者：
Tiano, Joseph P.;Delghingaro-Augusto, Viviane;Mauvais-Jarvis, Franck
通讯作者：
Mauvais-Jarvis, Franck