Novel insight into glucagon receptor action: lessons from knockout and transgenic mouse models.
Novel insight into glucagon receptor action: lessons from knockout and transgenic mouse models.
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DOI：
10.1111/j.1463-1326.2011.01447.x
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Charron MJ
中科院分区：
文献类型：
--
作者：
Vuguin PM;Charron MJ
使用基因敲除和转基因技术，转基因动物模型使我们能够了解胰高血糖素信号在代谢中的作用。使用基因靶向设计具有胰高血糖素受体基因（Gcgr）的整体缺失的小鼠。Gcgr−/−小鼠的表型为Gcgr在胎儿生长、胰腺发育以及葡萄糖和脂质稳态中的作用提供了重要线索。缺乏Gcgr激活与以下相关：（i）妊娠低血糖、胎儿生长不良和胎儿-新生儿死亡增加;（ii）胰岛细胞结构改变;（iii）葡萄糖、脂质和激素环境改变;（iv）胃排空减少;（v）身体组成改变和防止饮食诱导的肥胖;（vi）能量状态改变;（vii）肝细胞存活受损;（viii）改变对长时间禁食和运动的代谢反应和（ix）防止胰岛素缺乏小鼠中糖尿病的发展。相比之下，在胰腺β细胞上过表达Gcgr的小鼠显示出胰岛素分泌、胰腺胰岛素含量和β细胞质量的增加，并且在喂食高脂饮食时部分保护免于高血糖症和葡萄糖耐量受损。这些发现表明胰高血糖素信号传导在葡萄糖和脂质稳态的调节中起重要作用。旨在阻断Gcgr激活的治疗方案可能对糖尿病的治疗产生负面影响。
Using knockout and transgenic technology, genetically modified animal models allowed us to understand the role of glucagon signalling in metabolism. Mice with a global deletion of the glucagon receptor gene (Gcgr) were designed using gene targeting. The phenotype of Gcgr−/− mouse provided important clues about the role of Gcgr in foetal growth, pancreatic development and glucose and lipid homeostasis. The lack of Gcgr activation was associated with: (i) hypoglycaemic pregnancies, poor foetal growth and increased foetal–neonatal demise; (ii) altered cytoarchitecture of pancreatic islets; (iii) altered glucose, lipid and hormonal milieu; (iv) reduced gastric emptying; (v) altered body composition and protection from diet-induced obesity; (vi) altered energy state; (vii) impaired hepatocyte survival; (viii) altered metabolic response to prolonged fasting and exercise and (ix) prevented development of diabetes in insulin-deficient mice. In contrast, mice overexpressing the Gcgr on pancreatic β-cells displayed an increase insulin secretion, pancreatic insulin content and β-cell mass, and partially protected against hyperglycaemia and impaired glucose tolerance when fed a high-fat diet. These findings suggest that glucagon signalling plays a significant role in the regulation of glucose and lipid homeostasis. Treatment options designed to block Gcgr activation may have negative implications in the treatment of diabetes.
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影响因子：
3.5
作者：
BURCELIN, R;LI, J;CHARRON, MJ
通讯作者：
CHARRON, MJ
影响因子：
29
作者：
Longuet, Christine;Sinclair, Elaine M.;Drucker, Daniel J.
通讯作者：
Drucker, Daniel J.
DOI：
10.1073/pnas.131200398
发表时间：
2001-08-28
影响因子：
11.1
作者：
Jiang, YW;Cypess, AM;Sakmar, TP
通讯作者：
Sakmar, TP
影响因子：
7.7
作者：
Lee Y;Wang MY;Du XQ;Charron MJ;Unger RH
通讯作者：
Unger RH
影响因子：
8.2
作者：
de Heer, J.;Rasmussen, C.;Holst, J. J.
通讯作者：
Holst, J. J.