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The energy sensing LKB 1– AMPK α1 pathway regulates IGF 1 secretion and consequent activation of the IGF 1R– PKB pathway in primary hepatocytes
Author(s) -
Chen Liang,
Chen Qiaoli,
Rong Ping,
Wang Hong Yu,
Chen Shuai
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14106
Subject(s) - ampk , microbiology and biotechnology , protein kinase a , secretion , protein kinase b , signal transduction , pi3k/akt/mtor pathway , amp activated protein kinase , insulin like growth factor 1 receptor , chemistry , kinase , receptor , biology , endocrinology , growth factor , biochemistry
The insulin‐like growth factor 1 ( IGF 1) pathway has been linked with various diseases including diabetes, cancer and aging. In contrast to the well‐established regulatory mechanisms controlling IGF 1 expression, molecular mechanisms regulating its secretion are not fully understood. The AMP ‐activated protein kinase ( AMPK ) is a key energy sensor, and cumulative evidence shows that it is an attractive therapeutic target for treatment of diabetes, cancer and aging. Here we found that deficiency of AMPK promoted IGF 1 secretion in mouse primary hepatocytes. Furthermore, we found that AMPK α1 but not AMPK α2 was involved in regulation of IGF 1 secretion in mouse primary hepatocytes. Knockout of AMPK caused activation of the IGF 1 receptor ( IGF 1R)–protein kinase B ( PKB ; also known as Akt) pathway in hepatocytes, which was mediated by hypersecretion of IGF 1. Upstream of AMPK , liver kinase B1 ( LKB 1) was responsible for AMPK ‐dependent suppression of IGF 1 secretion in hepatocytes. Collectively, these findings demonstrate that the energy‐sensing LKB 1– AMPK pathway regulates IGF 1 secretion in mouse primary hepatocytes, which in turn regulates activation of the IGF 1R– PKB pathway.