GSK3β: A plausible molecular target in the cytokinemodulating effect of exogenous insulin in a murine model of malarial infection
https://doi.org/10.47665/tb.37.4.1105
- Author:
Aizuddin, N.N.F.
1
;
Ganesan, N.
1
;
Ng, W.C.
1
;
Ali, A.H.
1
;
Ibrahim, I.
1
;
Basir, R.
2
;
Embi, N.
1
;
Hasidah, M.S.
1
Author Information
1. Faculty of Science and Technology, Universiti Kebangsaan Malaysia
2. Pharmacology Unit, Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia
- Publication Type:Journal Article
- From:Tropical Biomedicine
2020;37(No.4):1105-1116
- CountryMalaysia
- Language:English
-
Abstract:
Malaria is a life-threatening disease caused by the Plasmodium sp. parasite.
Infection results in heightened pro-inflammatory response which contributes to the
pathophysiology of the disease. To mitigate the overwhelming cytokine response, host-directed
therapy is a plausible approach. Glycogen synthase kinase-3β (GSK3β), a serine/threonine
kinase plays a pivotal role in the regulation of inflammatory response during pathogenic
infections. The present study was conducted to investigate the chemo-suppressive and
cytokine-modulating effects of insulin administration in malaria-infected mice and the
involvement of GSK3β. Intraperitoneal administrations of 0.3 and 0.5 U/kg body weight
insulin each for four consecutive days into Plasmodium berghei NK65 (PbN)-infected mice
resulted in chemo-suppression exceeding 60% and improved median survival time of infected
mice (20.5 days and 19 days respectively compared to 15.5 days for non-treated control).
Western analysis revealed that pGSK3β (Ser9) intensity in brain samples from insulin-treated
(0.3 and 0.5 U/kg body weight) infected mice each were 0.6 and 2.2 times respectively than
that in control. In liver samples, pGSK3β (Ser9) intensity from insulin-treated infected mice
were significantly higher (4.8 and 16.1 fold for 0.3 and 0.5 U/kg bw respectively) than that in
control. Insulin administration decreased both brain and liver pNF-κB p65 (Ser536) intensities
(to 0.8 and 0.6 times for 0.3 U/kg bw insulin; and to 0.2 and 0.1 times for 0.5 U/kg bw insulin
respectively compared to control). Insulin treatment (0.5 U/kg bw) also significantly decreased
the serum levels of pro-inflammatory cytokines (TNF-α (3.3 times) and IFN-γ (4.9 times))
whilst significantly increasing the levels of anti-inflammatory cytokines (IL-4 (4.9 fold) and
IL-10 (2.1 fold)) in PbN-infected mice. Results from this study demonstrated that the cytokinemodulating effects of insulin at least in part involve inhibition of GSK3β and consequent
inhibition of the activation of NF-κB p65 suggesting insulin as a potential adjunctive therapeutic
for malaria.
- Full text:8.2020my1194.pdf
