PMID: 19662685Aug 8, 2009

Hepatic energy state is regulated by glucagon receptor signaling in mice

The Journal of Clinical Investigation
Eric D BerglundDavid H Wasserman


The hepatic energy state, defined by adenine nucleotide levels, couples metabolic pathways with energy requirements. This coupling is fundamental in the adaptive response to many conditions and is impaired in metabolic disease. We have found that the hepatic energy state is substantially reduced following exercise, fasting, and exposure to other metabolic stressors in C57BL/6 mice. Glucagon receptor signaling was hypothesized to mediate this reduction because increased plasma levels of glucagon are characteristic of metabolic stress and because this hormone stimulates energy consumption linked to increased gluconeogenic flux through cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) and associated pathways. We developed what we believe to be a novel hyperglucagonemic-euglycemic clamp to isolate an increment in glucagon levels while maintaining fasting glucose and insulin. Metabolic stress and a physiological rise in glucagon lowered the hepatic energy state and amplified AMP-activated protein kinase signaling in control mice, but these changes were abolished in glucagon receptor- null mice and mice with liver-specific PEPCK-C deletion. 129X1/Sv mice, which do not mount a glucagon response to hypoglycemia, displayed an increa...Continue Reading


Oct 1, 1976·Physiological Reviews·R H Unger, L Orci
Jan 14, 1977·European Journal of Applied Physiology and Occupational Physiology·H GalboN Bie
Jan 1, 1975·Journal of Applied Physiology·H GalboN J Christensen
May 1, 1985·Journal of Neuroscience Methods·I A Macdonald, D M Lake
Jan 1, 1974·The Journal of Clinical Endocrinology and Metabolism·J E GerichP H Forsham
Dec 1, 1970·The Journal of Clinical Investigation·E B MarlissG F Cahill
Jun 15, 1983·The Biochemical Journal·G L Dohm, E A Newsholme
Dec 1, 1983·Clinical Endocrinology·F P AlfordS Whitehouse
Mar 1, 1984·Diabetes·A A StarkeH Zimmermann
Apr 15, 1996·Archives of Biochemistry and Biophysics·N ErcanFrank Q Nuttall
Feb 4, 1999·Journal of Applied Physiology·C L Carlson, W W Winder
Mar 3, 1999·The Biochemical Journal·D Grahame HardieS P Davies
Aug 1, 2000·Archives of Physiology and Biochemistry·A Ghanbari-NiakiJ M Lavoie
Aug 11, 2000·Molecular and Cellular Biology·P SheMark A Magnuson
Aug 19, 2000·American Journal of Physiology. Endocrinology and Metabolism·M G KrishnaDavid H Wasserman
Oct 17, 2001·The Journal of Clinical Investigation·G ZhouD E Moller
Nov 17, 2001·Journal of Bioenergetics and Biomembranes·C BravoR Moreno-Sánchez
Dec 18, 2001·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·D Grahame Hardie, Simon A Hawley
Feb 21, 2002·The Journal of Biological Chemistry·Scott W NelsonHerbert J Fromm
Jun 18, 2002·American Journal of Physiology. Endocrinology and Metabolism·Nacide Ercan-FangFrank Q Nuttall
Jan 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·R W GellingMaureen J Charron
Feb 20, 2003·The American Journal of Gastroenterology·Satheesh NairAnna Mae Diehl
Mar 11, 2003·American Journal of Physiology. Endocrinology and Metabolism·Guoqiang Jiang, Bei B Zhang
May 1, 1962·Proceedings of the Society for Experimental Biology and Medicine·C R MORGAN, A LAZAROW
Nov 15, 2003·Current Biology : CB·Angela WoodsDavid Carling
Apr 8, 2004·American Journal of Physiology. Endocrinology and Metabolism·Kei SakamotoDario R Alessi
Sep 7, 2004·The Journal of Biological Chemistry·Shawn C BurgessA Dean Sherry
Oct 21, 2004·The Journal of Biological Chemistry·Scot R KimballLeonard S Jefferson
Jan 22, 2005·Science·Bradford B Lowell, Gerald I Shulman
May 14, 2005·Annals of the New York Academy of Sciences·G JanerC Porte
Jul 28, 2005·American Journal of Physiology. Endocrinology and Metabolism·Raul C CamachoDavid H Wasserman
Oct 13, 2005·American Journal of Physiology. Endocrinology and Metabolism·Raul C CamachoDavid H Wasserman
Apr 29, 2006·The Journal of Physiology·D Grahame HardieJohn W Scott
Sep 1, 2006·The Journal of Biological Chemistry·Marianne SuterDietbert Neumann
Dec 7, 2006·The Biochemical Journal·Matthew J SandersDavid Carling
May 15, 2007·The Journal of Physiology·Patrick T FuegerDavid H Wasserman
Aug 23, 2007·American Journal of Physiology. Endocrinology and Metabolism·Ditte K KleinJørgen F P Wojtaszewski
Nov 6, 2007·Frontiers in Bioscience : a Journal and Virtual Library·Sean L McGee, Mark Hargreaves
Mar 12, 2008·Liver International : Official Journal of the International Association for the Study of the Liver·Steven F SolgaJeanne M Clark
Apr 10, 2008·Diabetes·Eric D BerglundDavid H Wasserman
Aug 30, 2008·The Biochemical Journal·Sudheer K MantenaShannon M Bailey
Dec 3, 2008·Cell Metabolism·Christine LonguetDaniel J Drucker
Feb 7, 2009·The Biochemical Journal·Erik A Richter, Neil B Ruderman


Feb 25, 2011·Nature Reviews. Molecular Cell Biology·Judith Y Altarejos, Marc Montminy
Aug 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Young LeeR H Unger
Aug 17, 2011·Diabetes, Obesity & Metabolism·Patricia M Vuguin, Maureen J Charron
Aug 17, 2011·Diabetes, Obesity & Metabolism·Christopher J RamnananA D Cherrington
Aug 17, 2011·Diabetes, Obesity & Metabolism·Y Hayashi
Jul 29, 2010·American Journal of Physiology. Endocrinology and Metabolism·Eric D BerglundDavid H Wasserman
Mar 29, 2012·American Journal of Physiology. Endocrinology and Metabolism·I-Chen PengJohn Y-J Shyy
Nov 19, 2010·The Journal of Clinical Investigation·Noelia RiveraA D Cherrington
Jun 26, 2010·The Journal of Clinical Investigation·Russell A Miller, Morris J Birnbaum
Dec 24, 2010·The Journal of Experimental Biology·David H WassermanRobert S Lee-Young
May 1, 2012·Journal of Nutrition and Metabolism·Fábio S LiraMarília Seelaender
Aug 27, 2014·Proceedings of the National Academy of Sciences of the United States of America·Young LeeR H Unger
Apr 16, 2013·Annales d'endocrinologie·Benoit Viollet, Marc Foretz
Jul 17, 2012·Molecular and Cellular Endocrinology·Clinton M HasenourDavid H Wasserman
Jan 12, 2012·The Biochemical Journal·Laurent BultotMark H Rider
Jul 5, 2011·Cell Metabolism·Hua V Lin, Domenico Accili
Jan 9, 2015·The Journal of Endocrinology·Maureen J Charron, Patricia M Vuguin
Nov 5, 2014·European Journal of Applied Physiology·Roy J Shephard, Nathan Johnson
Apr 22, 2017·The Journal of Endocrinology·Caroline E Geisler, Benjamin J Renquist
Jul 5, 2017·Biochemical Society Transactions·Minnie Fu, Xiaoyong Yang
Feb 15, 2019·Brain and Behavior·Jin-Yong JoungChang-Gue Son
May 14, 2011·Journal of Applied Physiology·R Scott Rector, John P Thyfault
Aug 1, 2019·American Journal of Physiology. Cell Physiology·Lisa KellyMauricio Di Fulvio
Sep 11, 2014·American Journal of Physiology. Endocrinology and Metabolism·Greg M Kowalski, Clinton R Bruce
Apr 3, 2015·Physiological Reviews·Darleen A Sandoval, David A D'Alessio
Mar 12, 2020·FEBS Letters·Iliana López-SoldadoJoan J Guinovart
Apr 28, 2011·Endocrinology·Robby Zachariah TomMarie Björnholm
Sep 2, 2020·International Journal of Experimental Pathology·Milan Holeček, Melita Vodeničarovová
Aug 3, 2010·The Journal of Physiology·John P Thyfault, R Scott Rector
Feb 7, 2015·The Journal of Biological Chemistry·Kai LiFeifan Guo
May 10, 2019·Frontiers in Physiology·Katrine D GalsgaardNicolai J Wewer Albrechtsen
May 21, 2015·American Journal of Physiology. Endocrinology and Metabolism·Clinton M HasenourJamey D Young
Aug 29, 2014·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Sandra C RodriguesSilvana Bordin
Oct 31, 2018·Frontiers in Endocrinology·Hirokazu TakahashiKeizo Anzai

Related Concepts

Magnesium ADP
Adenosine Triphosphate, Chromium Ammonium Salt
Energy Metabolism
Mice, Inbred C57BL
GTP-Dependent Phosphoenolpyruvate Carboxykinase
Signal Transduction
Glucagon Receptor

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Synthetic Genetic Array Analysis

Synthetic genetic arrays allow the systematic examination of genetic interactions. Here is the latest research focusing on synthetic genetic arrays and their analyses.

Congenital Hyperinsulinism

Congenital hyperinsulinism is caused by genetic mutations resulting in excess insulin secretion from beta cells of the pancreas. Here is the latest research.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Epigenetic Memory

Epigenetic memory refers to the heritable genetic changes that are not explained by the DNA sequence. Find the latest research on epigenetic memory here.

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Femoral Neoplasms

Femoral Neoplasms are bone tumors that arise in the femur. Discover the latest research on femoral neoplasms here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.