The Impact of Low-Dose Insulin on Peripheral Nerve Insulin Receptor Signaling in Streptozotocin-Induced Diabetic RatsReportar como inadecuado




The Impact of Low-Dose Insulin on Peripheral Nerve Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Kazuhiro Sugimoto , Masayuki Baba, Susumu Suzuki, Soroku Yagihashi

Fuente: http://plos.srce.hr/



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