Alantolactone Improves Prolonged Exposure of Interleukin-6-InducedSkeletal Muscle Inflammation Associated Glucose Intolerance and InsulinResistance

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/474388.do
DOI
10.3389/fphar.2017.00405
Title
Alantolactone Improves Prolonged Exposure of Interleukin-6-InducedSkeletal Muscle Inflammation Associated Glucose Intolerance and InsulinResistance
Description
This work was supported by grants (NRF-2013R1A1A2A10005492 andMRC-2009-0083533) from the National Research Foundation of Korea.
abstract
The pro-inflammatory cytokine, Interleukin-6 (IL-6), has been proposed to be one of the mediators that link chronic inflammation to glucose intolerance and insulin resistance. Many studies have demonstrated the effects of IL-6 on insulin action in the skeletal muscle. However, few studies have investigated the effect of long-term treatment of IL-6, leading to glucose intolerance and insulin resistance. In the present study, we observed protective effects of alantolactone, a sesquiterpene lactone isolated from Inula helenium against glucose intolerance and insulin resistance induced by prolonged exposure of IL-6. Alantolactone has been reported to have anti-inflammatory and anti-cancer effects through IL-6-induced signal transducer and activator of transcription 3 (STAT3) signaling pathway. The relationship between IL-6 exposure and expression of toll-like receptor 4 (TLR4), involved in inflammation in the skeletal muscle, and the underlying mechanisms were investigated. We observed maximum dysregulation of glucose uptake after 40 ng/ml IL-6 induction for 24 h in L6 myotubes. Prolonged IL-6 exposure suppressed glucose uptake regulating alpha serine/threonine-protein kinase (AKT) phosphorylation; however, pretreatment with alantolactone activated AKT phosphorylation and improved glucose uptake. Alantolactone also attenuated IL-6-stimulated STAT3 phosphorylation, followed by an increase in expression of negative regulator suppressor of cytokine signaling 3 (SOCS3). Furthermore, IL-6-induced expression of pathogen recognition receptor, TLR4, was also suppressed by alantolactone pretreatment. Post-silencing of STAT3 using siRNA approach, IL-6-stimulated siRNA-STAT3 improved glucose uptake and suppressed TLR4 gene expression. Taken together, we propose that, as a STAT3 inhibitor, alantolactone, improves glucose regulation in the skeletal muscle by inhibiting IL-6-induced STAT3-SOCS3 signaling followed by inhibition of the TLR4 gene expression. Therefore, alantolactone can
provenance
Made available in Cube on 2018-09-28T10:44:44Z (GMT). No. of bitstreams: 0
language
English
author
Kim, Minjee
Song, Kwangho
Kim, Yeong Shik
accessioned
2018-09-28T10:44:44Z
available
2018-09-28T10:44:44Z
issued
2017
citation
FRONTIERS IN PHARMACOLOGY(8)
issn
1663-9812
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/474388.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345274046
Jurisdiction
Rep.of Korea
Project Name
Research & Educational Program for Creative Global Pharmaceutical Scientists (R&E Program for CGPS)
rights
openAccess
subject
alantolactone
sesquiterpenoids
glucose intolerance
inflammation
insulin resistance
diabetes
type
article


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