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Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity.

Abstract：

:Crosstalk between liver and skeletal muscle is vital for glucose homeostasis. Hepatokines, liver-derived proteins that play an important role in regulating muscle metabolism, are important to this communication. Here we identify apolipoprotein J (ApoJ) as a novel hepatokine targeting muscle glucose metabolism and insulin sensitivity through a low-density lipoprotein receptor-related protein-2 (LRP2)-dependent mechanism, coupled with the insulin receptor (IR) signaling cascade. In muscle, LRP2 is necessary for insulin-dependent IR internalization, an initial trigger for insulin signaling, that is crucial in regulating downstream signaling and glucose uptake. Of physiologic significance, deletion of hepatic ApoJ or muscle LRP2 causes insulin resistance and glucose intolerance. In patients with polycystic ovary syndrome and insulin resistance, pioglitazone-induced improvement of insulin action is associated with an increase in muscle ApoJ and LRP2 expression. Thus, the ApoJ-LRP2 axis is a novel endocrine circuit that is central to the maintenance of normal glucose homeostasis and insulin sensitivity.

journal_name

Nat Commun

journal_title

Nature communications

authors

Seo JA,Kang MC,Yang WM,Hwang WM,Kim SS,Hong SH,Heo JI,Vijyakumar A,Pereira de Moura L,Uner A,Huang H,Lee SH,Lima IS,Park KS,Kim MS,Dagon Y,Willnow TE,Aroda V,Ciaraldi TP,Henry RR,Kim YB

doi

10.1038/s41467-020-15963-w

subject

Has Abstract

pub_date

2020-04-24 00:00:00

pages

2024

issue

1

issn

2041-1723

pii

10.1038/s41467-020-15963-w

journal_volume

11

pub_type

临床试验,杂志文章

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