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Inflamm Res. 2018 Oct;67(10):863-877. doi: 10.1007/s00011-018-1177-0. Epub 2018 Aug 6.

Evaluation of neuroprotective effects of insulin on immuno-inflammatory and systemic disorders induced by kaliotoxin, a Kv1.3 channel blocker.

Author information

1
Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology, USTHB, BP 32, El-Alia, Bab Ezzouar, 16111, Algiers, Algeria.
2
CRN2M UMR 7286, CNRS, Aix Marseille Universite', 13344, Marseille Cedex 15, France.
3
Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology, USTHB, BP 32, El-Alia, Bab Ezzouar, 16111, Algiers, Algeria. flaraba@usthb.dz.

Abstract

OBJECTIVE:

Kaliotoxin2 (KTX2) is a highly selective blocker of voltage-dependent potassium channels Kv1.3 containing 37 amino acid residues. It is purified from Androctonus australis scorpion venom. The binding of KTX2 to its targets is able to alter the neuronal excitability leading to neurological disorders, accompanied by an inflammatory response. In brain, activation of insulin receptor signaling pathway by insulin induces current suppression and concomitant tyrosine phosphorylation of Kv1.3 channel. The aim of this study is to evaluate the effect of insulin injected by i.c.v. route on the neuro-pathophysiological and systemic disorders induced by KTX2.

MATERIALS AND METHODS:

Tissue damage, inflammatory response and oxidative stress biomarkers were assessed in NMRI mice at 24 h after co-injection of KTX2 and insulin by intracerebroventricular route.

RESULTS:

Obtained results revealed that the central administration of insulin prevents cerebral cortex injury, brain edema and blood-brain barrier alteration induced by KTX2, these are accompanied by significant decrease of systemic disorders including serum cytokines, inflammatory and oxidative stress markers and tissue damage.

CONCLUSION:

These results indicate that insulin is able to reduce neuro-immunological effects and systemic disorders induced by KTX2. The neuroprotective effect of insulin may be due to its crucial role in the regulation of inflammation response and its properties to modulate the activity of Kv1.3 channels in brain.

KEYWORDS:

Blood–brain barrier; Brain; Inflammatory response; Insulin; Kaliotoxin; Kv1.3 channels

PMID:
30083976
DOI:
10.1007/s00011-018-1177-0
[Indexed for MEDLINE]

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