title: Transcriptional profiling of diabetic neuropathy in the BKS db/db mouse: a model of type 2 diabetes.
abstract: OBJECTIVE
  A better understanding of the molecular mechanisms underlying the development and progression of diabetic neuropathy (DN) is essential for the design of mechanism-based therapies. We examined changes in global gene expression to define pathways regulated by diabetes in peripheral nerve.
  
  
  METHODS
  Microarray data for 24-week-old BKS db/db and db/+ mouse sciatic nerve were analyzed to define significantly differentially expressed genes (DEGs); DEGs were further analyzed to identify regulated biological processes and pathways. Expression profile clustering was performed to identify coexpressed DEGs. A set of coexpressed lipid metabolism genes was used for promoter sequence analysis.
  
  
  RESULTS
  Gene expression changes are consistent with structural changes of axonal degeneration. Pathways regulated in the db/db nerve include lipid metabolism, carbohydrate metabolism, energy metabolism, peroxisome proliferator-activated receptor signaling, apoptosis, and axon guidance. Promoter sequences of lipid metabolism-related genes exhibit evidence of coregulation of lipid metabolism and nervous system development genes.
  
  
  CONCLUSIONS
  Our data support existing hypotheses regarding hyperglycemia-mediated nerve damage in DN. Moreover, our analyses revealed a possible coregulation mechanism connecting hyperlipidemia and axonal degeneration.
authors: Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
authors: Manjusha
authors: M
authors: Pande
authors: Junguk
authors: J
authors: Hur
authors: Yu
authors: Y
authors: Hong
authors: Carey
authors: C
authors: Backus
authors: John M
authors: JM
authors: Hayes
authors: Sang Su
authors: SS
authors: Oh
authors: Matthias
authors: M
authors: Kretzler
authors: Eva L
authors: EL
authors: Feldman
references: Diabetologia. 2001 Nov;44(11):1973-88
references: 11719828
references: Diabetologia. 1996 Nov;39(11):1377-84
references: 8933008
references: Exp Neurol. 1994 Nov;130(1):106-14
references: 7821385
references: Pain. 1990 Jan;40(1):105-107
references: 2339005
references: Nat Rev Endocrinol. 2010 Jan;6(1):19-25
references: 19859073
references: Genes Dev. 2003 Oct 1;17(19):2450-64
references: 14522948
references: Acta Neuropathol. 2000 May;99(5):539-46
references: 10805099
references: Diabetes Care. 2003 Jun;26(6):1790-5
references: 12766111
references: Rev Endocr Metab Disord. 2004 Aug;5(3):227-36
references: 15211094
references: Acta Neuropathol. 2001 Apr;101(4):367-74
references: 11355308
references: Neuropathol Appl Neurobiol. 1980 Sep-Oct;6(5):361-74
references: 6969863
references: Philos Trans R Soc Lond B Biol Sci. 1996 Mar 29;351(1338):455-62
references: 8730785
references: Lab Invest. 1979 Jun;40(6):627-32
references: 449272
references: Metabolism. 2000 Jan;49(1):22-31
references: 10647060
references: Exp Neurol. 1984 Feb;83(2):221-32
references: 6692864
references: Nat Genet. 2006 May;38(5):500-1
references: 16642009
references: Diabetes. 1980 Jan;29(1):60-7
references: 6991317
references: Bioinformatics. 2009 Jan 1;25(1):137-8
references: 18812364
references: Nucleic Acids Res. 2005 Nov 10;33(20):e175
references: 16284200
references: Bioinformatics. 2006 Aug 15;22(16):1988-97
references: 16766561
references: Exp Neurol. 2003 Feb;179(2):188-99
references: 12618126
references: BMC Bioinformatics. 2006 Dec 19;7:538
references: 17177995
references: Diabetes. 2009 Oct;58(10):2376-85
references: 19592619
references: Endocr Rev. 2004 Aug;25(4):612-28
references: 15294884
references: Bioinformatics. 2004 Jan 1;20(1):105-14
references: 14693816
references: Bioinformatics. 2005 Jul 1;21(13):2933-42
references: 15860560
references: J Pharmacol Exp Ther. 1997 Oct;283(1):366-74
references: 9336345
references: Diabetologia. 2005 Mar;48(3):578-85
references: 15729579
references: Genome Biol. 2003;4(5):P3
references: 12734009
references: Trends Genet. 2002 Feb;18(2):60-3
references: 11818130
references: Clin Orthop Relat Res. 1993 Nov;(296):78-85
references: 8222454
references: Bioinformatics. 2010 Feb 15;26(4):456-63
references: 20007254
references: Acta Neuropathol. 1978 Feb 20;41(2):85-9
references: 636848
references: FASEB J. 2002 Nov;16(13):1738-48
references: 12409316
references: Diabetes Metab Res Rev. 2000 Nov-Dec;16(6):408-33
references: 11114101
references: J Neuropathol Exp Neurol. 2000 Sep;59(9):798-807
references: 11005260
references: Circ Res. 2009 Oct 23;105(9):886-96
references: 19762685
references: J Peripher Nerv Syst. 2009 Dec;14(4):257-67
references: 20021567
references: Pharmacol Ther. 2008 Oct;120(1):1-34
references: 18616962
references: Curr Drug Targets. 2008 Jan;9(1):3-13
references: 18220709
references: Brain Res. 1992 Mar 20;575(2):320-4
references: 1571789
references: Neuromuscul Disord. 2010 Mar;20(3):192-7
references: 20122829
references: Neurobiol Dis. 2007 Dec;28(3):276-85
references: 17804249
references: Trends Endocrinol Metab. 2000 Aug;11(6):212-7
references: 10878750
references: Neurosci Lett. 1999 Mar 26;263(2-3):81-4
references: 10213140
references: Circulation. 2005 May 31;111(21):2798-804
references: 15911707
references: Curr Opin Neurol. 1997 Oct;10(5):386-97
references: 9330884
references: Neurosci Lett. 1995 Nov 10;200(1):37-40
references: 8584261
references: Hum Gene Ther. 2009 Jul;20(7):715-27
references: 19374591