Expression of human apolipoprotein E4 reduces insulin-receptor substrate 1 expression and Akt phosphorylation in the ageing liver.pdf.pdf

FEBS Open Bio 4 (2014) 260–265
journal homepage: ate/febsopenbio
Expression of human apolipoprotein E4 reduces insulin-receptor
substrate 1 expression and Akt phosphorylation in the ageing liver
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Qi-Rui Ong, Elizabeth S. Chan, Mei-Li Lim, Boon-Seng Wong
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
article info abstract
Article history: The diabetic drug rosiglitazone was reported to improve glucose tolerance in insulin-resistant
Received 9 December 2013 ApoE3 but not ApoE4 knock-in mice. We therefore examined whether apolipoprotein E (ApoE)
Revised 6 February 2014 has genotype-specific effects on liver insulin function. At 12 weeks, no difference in liver insulin sig-
Accepted 24 February 2014
naling was detected between fasting ApoE3 and ApoE4 mice. At 72 weeks however, ApoE4 mice had
lower IRS-1 and PI3K expression, and reduced Akt phosphorylation. This decline was associated with
lower insulin and higher glucose in ApoE4 mouse liver. Liver cholesterol was not affected. These
results show that ApoE4 expression reduces liver insulin signaling and insulin levels, leading to
Keywords:
higher glucose content.
Liver insulin signaling
ApoE Ó 2014 The Authors. Published by Elsevier . on behalf of the Federation of European Biochemical Societies. This
Akt signaling is an open access article under