The energy sensing LKB1–AMPKα1 pathway regulates IGF1 secretion and consequent activation of the IGF1R–PKB pathway in primary hepatocytes. (29th May 2017)

• Record Type: Journal Article
• Authors: Chen, Liang; Chen, Qiaoli; Rong, Ping; Wang, Hong Yu; Chen, Shuai
• Is Part Of: FEBS journal. Volume 284:Number 13(2017)
• Page Start: 2096
• Page End: 2109
• Publication Date: 2017-05-29
• Subjects: AMPK -- IGF1 secretion -- IGF1R activation -- LKB1 -- phosphorylation; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.14106
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : The insulin‐like growth factor 1 (IGF1) pathway has been linked with various diseases including diabetes, cancer and aging. In contrast to the well‐established regulatory mechanisms controlling IGF1 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 IGF1 secretion in mouse primary hepatocytes. Furthermore, we found that AMPKα1 but not AMPKα2 was involved in regulation of IGF1 secretion in mouse primary hepatocytes. Knockout of AMPK caused activation of the IGF1 receptor (IGF1R)–protein kinase B (PKB; also known as Akt) pathway in hepatocytes, which was mediated by hypersecretion of IGF1. Upstream of AMPK, liver kinase B1 (LKB1) was responsible for AMPK‐dependent suppression of IGF1 secretion in hepatocytes. Collectively, these findings demonstrate that the energy‐sensing LKB1–AMPK pathway regulates IGF1 secretion in mouse primary hepatocytes, which in turn regulates activation of the IGF1R–PKB pathway. Abstract : Secretion of insulin‐like growth factor 1 (IGF1) in cells is regulated by their energy status. Deficiency of the energy‐sensing AMP‐activated protein kinase (AMPK) increases IGF1 secretion in primary hepatocytes, which consequently causes activation of the IGF1R‐protein kinase B (PKB) pathway.