The energy sensing LKB1-AMPKα1 pathway regulates IGF1 secretion and consequent activation of the IGF1R-PKB pathway in primary hepatocytes

The FEBS Journal
Liang ChenShuai Chen

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.

References

Jul 1, 1997·The Journal of Pediatrics·G S Campbell
Oct 17, 2001·The Journal of Clinical Investigation·G ZhouD E Moller
Nov 15, 2003·Current Biology : CB·Angela WoodsDavid Carling
Apr 26, 2005·BMJ : British Medical Journal·Josie M M EvansAndrew D Morris
May 4, 2005·Molecular Cell·Russell G JonesCraig B Thompson
Nov 13, 2007·The Biochemical Journal·Shuai ChenCarol Mackintosh
Apr 29, 2008·Molecular Cell·Dana M GwinnReuben J Shaw
Nov 26, 2008·Nature Reviews. Cancer·Michael Pollak
Oct 16, 2009·American Journal of Physiology. Cell Physiology·Boubacar BenzianeAlexander V Chibalin
Nov 4, 2009·The Journal of Clinical Investigation·Shlomo Melmed
May 5, 2011·Endocrinology·Emily J Gallagher, Derek LeRoith
Aug 30, 2011·Trends in Endocrinology and Metabolism : TEM·Shuai ChenCarol MacKintosh
Sep 8, 2011·Proceedings of the National Academy of Sciences of the United States of America·Hayley M O'NeillGregory R Steinberg
Feb 10, 2012·American Journal of Physiology. Endocrinology and Metabolism·Serge DucommunShuai Chen
Mar 23, 2012·Nature Reviews. Molecular Cell Biology·D Grahame HardieSimon A Hawley
Apr 5, 2012·Nature Reviews. Endocrinology·Bente K Pedersen, Mark A Febbraio
Apr 21, 2012·Science·Simon A HawleyD Grahame Hardie
Jun 12, 2013·Cell·Carlos López-OtínGuido Kroemer
Apr 15, 2014·Cell Metabolism·Kristopher BurkewitzWilliam B Mair
Jul 25, 2014·Biochemical Pharmacology·Brice SidPedro Buc Calderon
Dec 3, 2014·Cell Metabolism·Marc ForetzBenoit Viollet
Jul 21, 2015·Annals of Pediatric Endocrinology & Metabolism·Min Sun Kim, Dae-Yeol Lee
Oct 3, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wade T Iams, Christine M Lovly
Jun 17, 2016·Proceedings of the National Academy of Sciences of the United States of America·Liang ChenShuai Chen

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Citations

Aug 22, 2018·American Journal of Physiology. Endocrinology and Metabolism·Kensaku FukunagaKoji Murao
Dec 15, 2020·Frontiers in Endocrinology·Ger J StrousJan A Mol

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