title: IL-6 deficiency in mice neither impairs induction of metabolic genes in the liver nor affects blood glucose levels during fasting and moderately intense exercise.
abstract: OBJECTIVE
  Fasting and exercise are strong physiological stimuli for hepatic glucose production. IL-6 has been implicated in the regulation of gluconeogenic genes, but the results are contradictory and the relevance of IL-6 for fasting- and exercise-induced hepatic glucose production is not clear.
  
  
  METHODS
  Investigations were performed in rat hepatoma cells, and on C57Bl6 and Il6(-/-) mice under the following conditions: IL-6 stimulation/injection, non-exhaustive exercise (60 min run on a treadmill) and fasting for 16 h. Metabolite analysis, quantitative real-time PCR and immunoblotting were performed.
  
  
  RESULTS
  IL-6 stimulation of rat hepatoma cells led to higher glucose production. Injection of IL-6 in mice slightly increased hepatic Pepck (also known as Pck1) expression. Fasting of Il6(-/-) mice for 16 h did not alter glucose production compared with wild-type mice, since plasma glucose concentrations were similar and upregulation of phosphoenolpyruvate carboxykinase (PEPCK) and Pgc-1alpha (also known as Ppargc1a) expression was comparable. In the non-fasting state, Il6(-/-) mice showed a mild metabolic alteration including higher plasma glucose and insulin levels, lower NEFA concentrations and slightly increased hepatic PEPCK content. Moderately intense exercise resulted in elevated IL-6 plasma levels in wild-type mice. Despite that, plasma glucose, insulin, NEFA levels and hepatic glycogen content were not different in Il6(-/-) mice immediately after running, while expression of hepatic G6pc, Pgc-1alpha, Irs2 and Igfbp1 mRNA was similarly increased.
  
  
  CONCLUSIONS
  These data suggest that in mice IL-6 is not essential for physiologically increased glucose production during fasting or non-exhaustive exercise.
authors.affiliation: Department of Internal Medicine, Division of Pathobiochemistry and Clinical Chemistry, University of Tuebingen, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Fritsche
authors.forename: M
authors.initials: M
authors.lastname: Hoene
authors.forename: R
authors.initials: R
authors.lastname: Lehmann
authors.forename: H
authors.initials: H
authors.lastname: Ellingsgaard
authors.forename: A M
authors.initials: AM
authors.lastname: Hennige
authors.forename: A K
authors.initials: AK
authors.lastname: Pohl
authors.forename: H U
authors.initials: HU
authors.lastname: Häring
authors.forename: E D
authors.initials: ED
authors.lastname: Schleicher
authors.forename: C
authors.initials: C
authors.lastname: Weigert
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D005215:Fasting / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005943:Gluconeogenesis / Q000235:genetics; D006003:Glycogen / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D001786:Blood Glucose; D007328:Insulin; D015850:Interleukin-6; D012333:RNA, Messenger; D006003:Glycogen; D019764:Phosphoenolpyruvate Carboxykinase (ATP)
references.citation: FASEB J. 2004 Jun;18(9):992-4
references.pmid: 15059966
references.citation: Cell Metab. 2006 Apr;3(4):267-75
references.pmid: 16581004
references.citation: Endocrinology. 2004 Jun;145(6):2680-6
references.pmid: 14988384
references.citation: Diabetes. 2006 Dec;55 Suppl 2:S48-54
references.pmid: 17130644
references.citation: J Clin Endocrinol Metab. 1997 Dec;82(12):4167-70
references.pmid: 9398733
references.citation: J Physiol. 2003 Jan 1;546(Pt 1):299-305
references.pmid: 12509497
references.citation: J Appl Physiol (1985). 2005 Feb;98(2):477-81
references.pmid: 15448117
references.citation: Nat Med. 2004 Feb;10(2):168-74
references.pmid: 14716305
references.citation: J Biol Chem. 2006 Mar 17;281(11):7060-7
references.pmid: 16418171
references.citation: J Clin Endocrinol Metab. 2001 Mar;86(3):1154-9
references.pmid: 11238501
references.citation: Hepatology. 2002 Jan;35(1):40-8
references.pmid: 11786958
references.citation: Diabetologia. 2010 Mar;53(3):399-402
references.pmid: 20012010
references.citation: Mol Endocrinol. 2009 Jun;23(6):827-37
references.pmid: 19264844
references.citation: Am J Physiol Endocrinol Metab. 2006 Mar;290(3):E405-8
references.pmid: 16219665
references.citation: Cell Metab. 2007 Jun;5(6):438-49
references.pmid: 17550779
references.citation: Am J Physiol Endocrinol Metab. 2004 Jul;287(1):E182-7
references.pmid: 15191885
references.citation: Am J Physiol Endocrinol Metab. 2004 Oct;287(4):E616-21
references.pmid: 15149950
references.citation: Metabolism. 1995 Feb;44(2):145-6
references.pmid: 7869907
references.citation: Hepatology. 1994 Dec;20(6):1577-83
references.pmid: 7527006
references.citation: Diabetes. 2006 Oct;55(10):2688-97
references.pmid: 17003332
references.citation: J Appl Physiol (1985). 2009 Dec;107(6):1830-9
references.pmid: 19850730
references.citation: Anal Biochem. 1976 Mar;71(1):96-105
references.pmid: 1275237
references.citation: J Physiol. 2000 Nov 15;529 Pt 1:237-42
references.pmid: 11080265
references.citation: Annu Rev Nutr. 2007;27:329-45
references.pmid: 17465853
references.citation: Diabetes. 2007 Jun;56(6):1630-7
references.pmid: 17363741
references.citation: Science. 1996 Nov 22;274(5291):1379-83
references.pmid: 8910279
references.citation: Histochem Cell Biol. 2007 Oct;128(4):371-7
references.pmid: 17805558
references.citation: Diabetes Care. 2005 Aug;28(8):2007-12
references.pmid: 16043746
references.citation: Am J Physiol Endocrinol Metab. 2001 Apr;280(4):E650-6
references.pmid: 11254473
references.citation: Am J Physiol Cell Physiol. 2007 Sep;293(3):C1139-47
references.pmid: 17615159
references.citation: J Physiol. 2009 Jan 15;587(1):241-52
references.pmid: 19001047
references.citation: Mol Cell Biol. 2001 Jan;21(2):414-24
references.pmid: 11134330
references.citation: Am J Physiol. 1990 Jan;258(1 Pt 1):E57-64
references.pmid: 2105658
references.citation: FASEB J. 2003 Nov;17(14):2166-8
references.pmid: 12958150
references.citation: Biochem Biophys Res Commun. 1990 Jun 15;169(2):623-8
references.pmid: 2357222
references.citation: Am J Physiol. 1997 Aug;273(2 Pt 1):E262-7
references.pmid: 9277378
references.citation: Biochem J. 2003 Aug 15;374(Pt 1):1-20
references.pmid: 12773095
references.citation: Mol Endocrinol. 2006 Dec;20(12):3364-75
references.pmid: 16945991
references.citation: Nat Med. 2002 Jan;8(1):75-9
references.pmid: 11786910
references.citation: J Clin Endocrinol Metab. 2003 Jul;88(7):3005-10
references.pmid: 12843134
references.citation: Eur J Appl Physiol. 2010 Feb;108(3):557-66
references.pmid: 19865828
references.citation: Diabetes. 2004 Jul;53(7):1643-8
references.pmid: 15220185
references.citation: Adv Exp Med Biol. 1998;441:117-27
references.pmid: 9781319
references.citation: Cell Metab. 2008 Jul;8(1):49-64
references.pmid: 18590692
references.citation: JAMA. 2001 Jul 18;286(3):327-34
references.pmid: 11466099
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13163-8
references.pmid: 18719127
references.citation: Hepatology. 2001 Jun;33(6):1377-86
references.pmid: 11391526