Enhanced glucose tolerance in pancreatic-derived factor (PANDER) knockout C57BL/6 mice.
Enhanced glucose tolerance in pancreatic-derived factor (PANDER) knockout C57BL/6 mice.
复制标题
DOI：
10.1242/dmm.016402
复制
发表时间：
2014-11
影响因子：
4.3
通讯作者：
Burkhardt BR
中科院分区：
文献类型：
--
作者：
Moak SL;Dougan GC;MarElia CB;Danse WA;Fernandez AM;Kuehl MN;Athanason MG;Burkhardt BR
胰源性因子（PANDER；也称为 FAM3B）是一种结构独特的蛋白质，在内分泌胰腺内强烈表达并分泌。 PANDER 被假设可以调节空腹和餐后葡萄糖稳态、肝脂肪生成和胰岛素信号传导，并在 2 型糖尿病 (T2D) 的发病或进展中发挥潜在作用。尽管在血糖调节和 T2D 中具有潜在的关键多效性作用，但用于研究 PANDER 功能的稳定动物模型的产生有限，并且没有针对 T2D 的成熟遗传小鼠背景的模型。我们的目标是生成增强的小鼠模型，以进一步阐明 PANDER 的生物学功能。因此，创建了纯种 PANDER 敲除 C57BL/6 (PANKO-C57) 模型，并对其血糖调节和肝脏胰岛素信号传导进行了表型表征。 PANKO-C57 模型表现出增强的代谢表型，特别是在增强的葡萄糖耐量方面。与匹配的 C57BL/6J 野生型小鼠相比，雄性 PANKO-C57 小鼠的空腹血浆胰岛素和 C 肽水平降低，而瘦素水平升高。尽管两组之间的外周胰岛素敏感性相似，但肝脏 PKB/Akt 和 AMPK 磷酸化增加以及成熟 SREBP-1 表达增加表明，禁食条件下肝脏胰岛素信号传导显着增加。与野生型 C57BL/6 小鼠相比，PANKO-C57 小鼠的胰岛素刺激导致肝甘油三酯和糖原含量增加。总之，PANKO-C57 小鼠代表了研究 PANDER 在多种代谢状态下的合适模型，并为阐明 PANDER 的生物学功能和在 T2D 中的潜在作用提供了额外的工具。
Pancreatic-derived factor (PANDER; also known as FAM3B) is a uniquely structured protein strongly expressed within and secreted from the endocrine pancreas. PANDER has been hypothesized to regulate fasting and fed glucose homeostasis, hepatic lipogenesis and insulin signaling, and to serve a potential role in the onset or progression of type 2 diabetes (T2D). Despite having potentially pivotal pleiotropic roles in glycemic regulation and T2D, there has been limited generation of stable animal models for the investigation of PANDER function, and there are no models on well-established genetic murine backgrounds for T2D. Our aim was to generate an enhanced murine model to further elucidate the biological function of PANDER. Therefore, a pure-bred PANDER knockout C57BL/6 (PANKO-C57) model was created and phenotypically characterized with respect to glycemic regulation and hepatic insulin signaling. The PANKO-C57 model exhibited an enhanced metabolic phenotype, particularly with regard to enhanced glucose tolerance. Male PANKO-C57 mice displayed decreased fasting plasma insulin and C-peptide levels, whereas leptin levels were increased as compared with matched C57BL/6J wild-type mice. Despite similar peripheral insulin sensitivity between both groups, hepatic insulin signaling was significantly increased during fasting conditions, as demonstrated by increased phosphorylation of hepatic PKB/Akt and AMPK, along with mature SREBP-1 expression. Insulin stimulation of PANKO-C57 mice resulted in increased hepatic triglyceride and glycogen content as compared with wild-type C57BL/6 mice. In summary, the PANKO-C57 mouse represents a suitable model for the investigation of PANDER in multiple metabolic states and provides an additional tool to elucidate the biological function and potential role in T2D.
登录
查看更多内容
在四种常用的近交小鼠菌株中的体内葡萄糖代谢。
影响因子：
7.7
作者：
Berglund, Eric D.;Li, Candice Y.;Poffenberger, Greg;Ayala, Julio E.;Fueger, Patrick T.;Willis, Shannon E.;Jewell, Marybeth M.;Powers, Alvin C.;Wasserman, David H.
通讯作者：
Wasserman, David H.
DOI：
10.1007/978-1-59745-471-1_23
发表时间：
2009
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Doetschman, Thomas
通讯作者：
Doetschman, Thomas
DOI：
10.1016/j.bbaexp.2005.07.003
发表时间：
2005-09-25
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Burkhardt, BR;Yang, MC;Wolf, BA
通讯作者：
Wolf, BA
胰源性因子促进小鼠肝脏脂肪生成：Forkhead Box 1 信号通路的作用
影响因子：
13.5
作者：
Li, Jing;Chi, Yujing;Guan, Youfei
通讯作者：
Guan, Youfei
影响因子：
29
作者：
Biddinger, Sudha B.;Hernandez-Ono, Antonio;Kahn, C. Ronald
通讯作者：
Kahn, C. Ronald