Inhibition of MEK1 Signaling Pathway in the Liver Ameliorates Insulin Resistance
Joint Authors
Ueyama, Atsunori
Ban, Nobuhiro
Fukazawa, Masanori
Hirayama, Tohru
Takeda, Minako
Yata, Tatsuo
Muramatsu, Hiroyasu
Hoshino, Masaki
Yamamoto, Marii
Matsuo, Masao
Kawashima, Yuka
Iwase, Tatsuhiko
Kitazawa, Takehisa
Kushima, Youichi
Yamada, Yuichiro
Kawabe, Yoshiki
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-12-28
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Although mitogen-activated protein kinase kinase (MEK) is a key signaling molecule and a negative regulator of insulin action, it is still uncertain whether MEK can be a therapeutic target for amelioration of insulin resistance (IR) in type 2 diabetes (T2D) in vivo.
To clarify whether MEK inhibition improves T2D, we examined the effect of continuous MEK inhibition with two structurally different MEK inhibitors, RO5126766 and RO4987655, in mouse models of T2D.
RO5126766 and RO4987655 were administered via dietary admixture.
Both compounds decreased blood glucose and improved glucose tolerance in doses sufficient to sustain inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation downstream of MEK in insulin-responsive tissues in db/db mice.
A hyperinsulinemic-euglycemic clamp test showed increased glucose infusion rate (GIR) in db/db mice treated with these compounds, and about 60% of the increase was attributed to the inhibition of endogenous glucose production, suggesting that the liver is responsible for the improvement of IR.
By means of adenovirus-mediated Mek1 shRNA expression, we confirmed that blood glucose levels are reduced by suppression of MEK1 expression in the liver of db/db mice.
Taken together, these results suggested that the MEK signaling pathway could be a novel therapeutic target for novel antidiabetic agents.
American Psychological Association (APA)
Ueyama, Atsunori& Ban, Nobuhiro& Fukazawa, Masanori& Hirayama, Tohru& Takeda, Minako& Yata, Tatsuo…[et al.]. 2015. Inhibition of MEK1 Signaling Pathway in the Liver Ameliorates Insulin Resistance. Journal of Diabetes Research،Vol. 2016, no. 2016, pp.1-13.
https://search.emarefa.net/detail/BIM-1108272
Modern Language Association (MLA)
Ueyama, Atsunori…[et al.]. Inhibition of MEK1 Signaling Pathway in the Liver Ameliorates Insulin Resistance. Journal of Diabetes Research No. 2016 (2016), pp.1-13.
https://search.emarefa.net/detail/BIM-1108272
American Medical Association (AMA)
Ueyama, Atsunori& Ban, Nobuhiro& Fukazawa, Masanori& Hirayama, Tohru& Takeda, Minako& Yata, Tatsuo…[et al.]. Inhibition of MEK1 Signaling Pathway in the Liver Ameliorates Insulin Resistance. Journal of Diabetes Research. 2015. Vol. 2016, no. 2016, pp.1-13.
https://search.emarefa.net/detail/BIM-1108272
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1108272