Glucagon contributes to liver zonation

被引：67

作者：

Cheng, Xiping ^{[1
]}

Kim, Sun Y. ^{[1
]}

Okamoto, Haruka ^{[1
]}

Xin, Yurong ^{[1
]}

Yancopoulos, George D. ^{[1
]}

Murphy, Andrew J. ^{[1
]}

Gromada, Jesper ^{[1
]}

机构：

[1] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2018年 / 115卷 / 17期

关键词：

glucagon; glucagon receptor; liver zonation; Wnt; ALPHA-CELL HYPERPLASIA; RECEPTOR KNOCKOUT MICE; WNT/BETA-CATENIN; BLOOD-GLUCOSE; METABOLISM; EXPRESSION; GENE; LGR5; GLUTAMINE;

D O I：

10.1073/pnas.1721403115

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Liver zonation characterizes the separation of metabolic pathways along the lobules and is required for optimal function. Wnt/beta-catenin signaling controls metabolic zonation by activating genes in the perivenous hepatocytes, while suppressing genes in the periportal counterparts. We now demonstrate that glucagon opposes the actions of Wnt/beta-catenin signaling on gene expression and metabolic zonation pattern. The effects were more pronounced in the periportal hepatocytes where 28% of all genes were activated by glucagon and inhibited by Wnt/beta-catenin. The glucagon and Wnt/beta-catenin receptors and their signaling pathways are uniformly distributed in periportal and perivenous hepatocytes and the expression is not regulated by the opposing signal. Collectively, our results show that glucagon controls gene expression and metabolic zonation in the liver through a counterplay with the Wnt/beta-catenin signaling pathway.

引用

收藏

页码：E4111 / E4119

页数：9

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