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

Qi-Rui Ong; Elizabeth S Chan; Mei-Li Lim; Boon-Seng Wong

doi:10.1016/j.fob.2014.02.011

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

FEBS Open Bio. 2014 Feb 28:4:260-5. doi: 10.1016/j.fob.2014.02.011. eCollection 2014.

Authors

Qi-Rui Ong¹, Elizabeth S Chan¹, Mei-Li Lim¹, Boon-Seng Wong¹

Affiliation

¹ Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Abstract

The diabetic drug rosiglitazone was reported to improve glucose tolerance in insulin-resistant ApoE3 but not ApoE4 knock-in mice. We therefore examined whether apolipoprotein E (ApoE) has genotype-specific effects on liver insulin function. At 12 weeks, no difference in liver insulin signaling 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 higher glucose content.

Keywords: Ageing; Akt signaling; ApoE; BCA, bicinchoninic acid; BSA, bovine serum albumin; ELISA, enzyme-linked immunosorbent assay; HRP, horseradish peroxidase; IRS-1, Insulin receptor substrate-1; KI, knock-in; Liver insulin signaling; PI3K, phosphatidylinositol 3-kinase.