title: Peripheral nervous system insulin resistance in ob/ob mice.
abstract: BACKGROUND
  A reduction in peripheral nervous system (PNS) insulin signaling is a proposed mechanism that may contribute to sensory neuron dysfunction and diabetic neuropathy. Neuronal insulin resistance is associated with several neurological disorders and recent evidence has indicated that dorsal root ganglion (DRG) neurons in primary culture display altered insulin signaling, yet in vivo results are lacking. Here, experiments were performed to test the hypothesis that the PNS of insulin-resistant mice displays altered insulin signal transduction in vivo. For these studies, nondiabetic control and type 2 diabetic ob/ob mice were challenged with an intrathecal injection of insulin or insulin-like growth factor 1 (IGF-1) and downstream signaling was evaluated in the DRG and sciatic nerve using Western blot analysis.
  
  
  RESULTS
  The results indicate that insulin signaling abnormalities documented in other "insulin sensitive" tissues (i.e. muscle, fat, liver) of ob/ob mice are also present in the PNS. A robust increase in Akt activation was observed with insulin and IGF-1 stimulation in nondiabetic mice in both the sciatic nerve and DRG; however this response was blunted in both tissues from ob/ob mice. The results also suggest that upregulated JNK activation and reduced insulin receptor expression could be contributory mechanisms of PNS insulin resistance within sensory neurons.
  
  
  CONCLUSIONS
  These findings contribute to the growing body of evidence that alterations in insulin signaling occur in the PNS and may be a key factor in the pathogenesis of diabetic neuropathy.
authors.affiliation: Department of Anatomy and Cell Biology, the University of Kansas Medical Center, Kansas City, KS 66160, USA. dwright@kumc.edu.
authors.forename: Caleb W
authors.initials: CW
authors.lastname: Grote
authors.forename: Anna L
authors.initials: AL
authors.lastname: Groover
authors.forename: Janelle M
authors.initials: JM
authors.lastname: Ryals
authors.forename: Paige C
authors.initials: PC
authors.lastname: Geiger
authors.forename: Eva L
authors.initials: EL
authors.lastname: Feldman
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Wright
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000503:physiopathology; D005727:Ganglia, Spinal / Q000503:physiopathology*; D006930:Hyperalgesia / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D008822:Mice, Transgenic; D051058:Oncogene Protein v-akt / Q000378:metabolism; D017288:Pain Threshold; D012584:Sciatic Nerve / Q000503:physiopathology*; D014110:Touch
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D051058:Oncogene Protein v-akt; D048031:JNK Mitogen-Activated Protein Kinases