PMID- 21754917
OWN - NLM
STAT- MEDLINE
DCOM- 20111103
LR  - 20211020
IS  - 1687-5303 (Electronic)
IS  - 1687-5214 (Print)
IS  - 1687-5214 (Linking)
VI  - 2011
DP  - 2011
TI  - Insulin receptor substrate 2 expression and involvement in neuronal insulin 
      resistance in diabetic neuropathy.
PG  - 212571
LID - 10.1155/2011/212571 [doi]
LID - 212571
AB  - Insulin signaling depends on tyrosine phosphorylation of insulin receptor 
      substrates (IRSs) to mediate downstream effects; however, elevated serine 
      phosphorylation of IRS impairs insulin signaling. Here, we investigated IRS 
      protein expression patterns in dorsal root ganglia (DRG) of mice and whether 
      their signaling was affected by diabetes. Both IRS1 and IRS2 are expressed in 
      DRG; however, IRS2 appears to be the prevalent isoform and is expressed by many 
      DRG neuronal subtypes. Phosphorylation of Ser(731)IRS2 was significantly elevated 
      in DRG neurons from type 1 and type 2 diabetic mice. Additionally, Akt activation 
      and neurite outgrowth in response to insulin were significantly decreased in DRG 
      cultures from diabetic ob/ob mice. These results suggest that DRG neurons express 
      IRS proteins that are altered by diabetes similar to other peripheral tissues, 
      and insulin signaling downstream of the insulin receptor may be impaired in 
      sensory neurons and contribute to the pathogenesis of diabetic neuropathy.
FAU - Grote, C W
AU  - Grote CW
AD  - Department of Anatomy and Cell Biology, The University of Kansas Medical Center, 
      Kansas City, KS 66160, USA.
FAU - Morris, J K
AU  - Morris JK
FAU - Ryals, J M
AU  - Ryals JM
FAU - Geiger, P C
AU  - Geiger PC
FAU - Wright, D E
AU  - Wright DE
LA  - eng
GR  - P20 RR016475/RR/NCRR NIH HHS/United States
GR  - P20 GM103418/GM/NIGMS NIH HHS/United States
GR  - P30 HD 002528/HD/NICHD NIH HHS/United States
GR  - R01 AG031575/AG/NIA NIH HHS/United States
GR  - P30 HD002528/HD/NICHD NIH HHS/United States
GR  - R01 NS043314/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110615
PL  - United States
TA  - Exp Diabetes Res
JT  - Experimental diabetes research
JID - 101274844
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs2 protein, mouse)
RN  - 0 (Leptin)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Experimental/chemically induced/*complications
MH  - Diabetic Neuropathies/*metabolism/*physiopathology
MH  - Disease Models, Animal
MH  - Ganglia, Spinal/metabolism
MH  - Insulin/metabolism/pharmacology
MH  - Insulin Receptor Substrate Proteins/*metabolism
MH  - Insulin Resistance/genetics/*physiology
MH  - Leptin/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurites/drug effects
MH  - Neurons/*metabolism
MH  - Obesity/genetics/metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/*physiology
MH  - Streptozocin/adverse effects
PMC - PMC3132877
EDAT- 2011/07/15 06:00
MHDA- 2011/11/04 06:00
PMCR- 2011/06/15
CRDT- 2011/07/15 06:00
PHST- 2010/12/31 00:00 [received]
PHST- 2011/03/22 00:00 [revised]
PHST- 2011/04/15 00:00 [accepted]
PHST- 2011/07/15 06:00 [entrez]
PHST- 2011/07/15 06:00 [pubmed]
PHST- 2011/11/04 06:00 [medline]
PHST- 2011/06/15 00:00 [pmc-release]
AID - 10.1155/2011/212571 [doi]
PST - ppublish
SO  - Exp Diabetes Res. 2011;2011:212571. doi: 10.1155/2011/212571. Epub 2011 Jun 15.