title: The impact of low-dose insulin on peripheral nerve insulin receptor signaling in streptozotocin-induced diabetic rats.
abstract: BACKGROUND
  The precise mechanisms of the neuroprotective effects of insulin in streptozotocin (STZ)-induced diabetic animals remain unknown, but altered peripheral nerve insulin receptor signaling due to insulin deficiency might be one cause.
  
  
  RESULTS
  Diabetes was induced in 10-week-old, male Wistar rats by injecting them with STZ (45 mg/kg). They were assigned to one group that received half of an insulin implant (∼1 U/day; I-group, n = 11) or another that remained untreated (U-group, n = 10) for 6 weeks. The controls were age- and sex-matched, non-diabetic Wistar rats (C-group, n = 12). Low-dose insulin did not change haemoglobin A1c, which increased by 136% in the U-group compared with the C-group. Thermal hypoalgesia and mechanical hyperalgesia developed in the U-group, but not in the I-group. Sensory and motor nerve conduction velocities decreased in the U-group, whereas sensory nerve conduction velocity increased by 7% (p = 0.0351) in the I-group compared with the U-group. Western blots showed unaltered total insulin receptor (IR), but a 31% decrease and 3.1- and 4.0-fold increases in phosphorylated IR, p44, and p42 MAPK protein levels, respectively, in sciatic nerves from the U-group compared with the C-group. Phosphorylated p44/42 MAPK protein decreased to control levels in the I-group (p<0.0001).
  
  
  CONCLUSIONS
  Low-dose insulin deactivated p44/42 MAPK and ameliorated peripheral sensory nerve dysfunction in rats with STZ-induced diabetes. These findings support the notion that insulin deficiency per se introduces impaired insulin receptor signaling in type 1 diabetic neuropathy.
authors.affiliation: Department of Laboratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan ; Diabetes Center, Ohta Nishinouchi Hospital, Koriyama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Baba
authors.forename: Susumu
authors.initials: S
authors.lastname: Suzuki
authors.forename: Soroku
authors.initials: S
authors.lastname: Yagihashi
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D009431:Neural Conduction / Q000187:drug effects; D059225:Nociception / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism*; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D007328:Insulin; D011972:Receptor, Insulin; D048052:Mitogen-Activated Protein Kinase 3
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