title: SOD1-G93A mice exhibit muscle-fiber-type-specific decreases in glucose uptake in the absence of whole-body changes in metabolism.
abstract: BACKGROUND
  Skeletal muscles play an important role in systemic glucose homeostasis and are purported to be the origin of the altered metabolic state observed in amyotrophic lateral sclerosis (ALS).
  
  
  OBJECTIVE
  The purpose of this study was to evaluate whole-body and muscle-specific glucose metabolism in the SOD1-G93A mouse model of ALS.
  
  
  METHODS
  We assessed glucose tolerance in early-, middle-, and late-stage SOD1-G93A and control mice using an intraperitoneal glucose tolerance test. We then measured the respiratory exchange ratio (CO2 production/O2 consumption) as a function of fasting and feeding using indirect calorimetry in a subset of male mice at these time points. Finally, muscles from all mice were harvested to evaluate basal and insulin-stimulated glucose transport in fast- and slow-twitch muscles.
  
  
  RESULTS
  No changes in systemic glucose clearance were observed in SOD1-G93A mice at any stage, nor were there changes in fasting insulin levels. Indirect calorimetry revealed an increase in the respiratory exchange ratio during the fed state at middle, but not at early or late stages of disease. Middle-stage SOD1-G93A mice exhibited decreased insulin-stimulated glucose uptake in fast-twitch, but not slow-twitch, skeletal muscle. Late-stage SOD1-G93A mice exhibited decreased insulin-stimulated glucose uptake in both fast- and slow-twitch muscle, as well as increased basal (non-insulin-stimulated) glucose uptake.
  
  
  CONCLUSIONS
  These results suggest that alterations in muscle metabolism occur in a fiber-type-specific manner in ALS, but do not necessarily lead to whole-body metabolic changes in SOD1-G93A mice.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kans., USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Smittkamp
authors.forename: Jill K
authors.initials: JK
authors.lastname: Morris
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Bomhoff
authors.forename: Mark E
authors.initials: ME
authors.lastname: Chertoff
authors.forename: Paige C
authors.initials: PC
authors.lastname: Geiger
authors.forename: John A
authors.initials: JA
authors.lastname: Stanford
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D002153:Calorimetry, Indirect; D004195:Disease Models, Animal; D018450:Disease Progression; D005215:Fasting / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D007328:Insulin; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D005947:Glucose
references.citation: Muscle Nerve. 2006 Jun;33(6):809-16
references.pmid: 16583367
references.citation: Clin Sci (Lond). 1983 Jun;64(6):601-9
references.pmid: 6340918
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19546-51
references.pmid: 17164329
references.citation: Science. 1994 Jun 17;264(5166):1772-5
references.pmid: 8209258
references.citation: Neurodegener Dis. 2005;2(3-4):202-7
references.pmid: 16909026
references.citation: Amyotroph Lateral Scler. 2010;11(1-2):166-71
references.pmid: 20184518
references.citation: Acta Neurol Scand. 1964;40(1):47-57
references.pmid: 14108417
references.citation: Neurology. 1968 Sep;18(9):915-25
references.pmid: 4301063
references.citation: J Pharmacol Exp Ther. 2001 Oct;299(1):314-22
references.pmid: 11561094
references.citation: Neurology. 1967 Feb;17(2):112-6
references.pmid: 6066871
references.citation: Physiol Genomics. 2008 Jan 17;32(2):207-18
references.pmid: 18000159
references.citation: Cell Metab. 2008 Nov;8(5):425-36
references.pmid: 19046573
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):11159-64
references.pmid: 15263088
references.citation: Neurobiol Dis. 2010 Oct;40(1):245-50
references.pmid: 20573565
references.citation: Neuroscience. 2008 Jan 24;151(2):613-21
references.pmid: 18061359
references.citation: J Neurol Neurosurg Psychiatry. 1977 Jun;40(6):533-7
references.pmid: 903768
references.citation: J Biol Chem. 1996 Sep 20;271(38):23111-6
references.pmid: 8798502
references.citation: N Engl J Med. 2001 May 31;344(22):1688-700
references.pmid: 11386269
references.citation: Neurobiol Dis. 2007 Nov;28(2):154-64
references.pmid: 17766128
references.citation: J Neurol Sci. 1975 Jun;25(2):205-10
references.pmid: 1151433
references.citation: Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5709-14
references.pmid: 8650157
references.citation: Antioxid Redox Signal. 2005 Nov-Dec;7(11-12):1553-67
references.pmid: 16356119
references.citation: Diabetes. 2009 Mar;58(3):567-78
references.pmid: 19073766
references.citation: Neuromuscul Disord. 2001 Nov;11(8):722-7
references.pmid: 11595514
references.citation: J Neurosci. 2000 Apr 1;20(7):2534-42
references.pmid: 10729333
references.citation: Amyotroph Lateral Scler Other Motor Neuron Disord. 2005 Mar;6(1):55-62
references.pmid: 16036427
references.citation: J Appl Physiol (1985). 2007 Mar;102(3):926-32
references.pmid: 17110520
references.citation: Proc R Soc Med. 1958 Oct;51(10):859-63
references.pmid: 13601739
references.citation: Muscle Nerve. 1997 Jan;20(1):45-51
references.pmid: 8995582
references.citation: Nat Neurosci. 2006 Mar;9(3):408-19
references.pmid: 16474388
references.citation: Metabolism. 1964 Nov;13:1376-81
references.pmid: 14241228
references.citation: Prog Neurobiol. 2008 May;85(1):94-134
references.pmid: 18282652
references.citation: Free Radic Biol Med. 2010 Apr 1;48(7):915-23
references.pmid: 20079427
references.citation: Am J Clin Nutr. 2001 Sep;74(3):328-34
references.pmid: 11522556
references.citation: Am J Physiol Endocrinol Metab. 2004 Oct;287(4):E739-43
references.pmid: 15165992
references.citation: J Clin Invest. 1985 Jul;76(1):149-55
references.pmid: 3894418
references.citation: Brain Res. 2003 Aug 22;982(1):92-7
references.pmid: 12915243
references.citation: Acta Neuropathol. 2003 Dec;106(6):561-8
references.pmid: 14517684
references.citation: Neuroreport. 1998 Mar 30;9(5):775-8
references.pmid: 9579663
references.citation: Diabetes Care. 2004 Jun;27(6):1487-95
references.pmid: 15161807
references.citation: Proc R Soc Med. 1962 Dec;55:1023-4
references.pmid: 14024223
references.citation: Am J Physiol Regul Integr Comp Physiol. 2007 Sep;293(3):R1159-68
references.pmid: 17584954
references.citation: Behav Brain Res. 2010 Jul 29;211(1):48-57
references.pmid: 20211206
references.citation: Neurology. 1969 Feb;19(2):185-9
references.pmid: 5812612
references.citation: Neuroreport. 2003 May 23;14(7):1051-4
references.pmid: 12802201
references.citation: Acta Neurol Scand. 1984 Dec;70(6):451-5
references.pmid: 6516795
references.citation: Diabetes. 2008 Jan;57(1):13-23
references.pmid: 17914033
references.citation: Neuroscience. 2005;130(4):897-910
references.pmid: 15652988
references.citation: Am J Physiol Endocrinol Metab. 2002 Sep;283(3):E413-22
references.pmid: 12169433
references.citation: J Neurol Sci. 1984 Mar;63(3):317-24
references.pmid: 6374040
references.citation: Dysphagia. 2009 Jun;24(2):180-95
references.pmid: 19107538