Format

Send to

Choose Destination
PLoS One. 2013 Aug 30;8(8):e74247. doi: 10.1371/journal.pone.0074247. eCollection 2013.

The impact of low-dose insulin on peripheral nerve insulin receptor signaling in streptozotocin-induced diabetic rats.

Author information

1
Department of Laboratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan ; Diabetes Center, Ohta Nishinouchi Hospital, Koriyama, Japan.

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.

METHODOLOGY AND PRINCIPAL FINDINGS:

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 AND SIGNIFICANCE:

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.

PMID:
24023699
PMCID:
PMC3758356
DOI:
10.1371/journal.pone.0074247
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center