Abstract：
:Proper control of hepatic glucose production is central to whole-body glucose homeostasis, and its disruption plays a major role in diabetes. Here, we demonstrate that although established as an intracellular lipid chaperone, aP2 is in fact actively secreted from adipocytes to control liver glucose metabolism. Secretion of aP2 from adipocytes is regulated by fasting- and lipolysis-related signals, and circulating aP2 levels are markedly elevated in mouse and human obesity. Recombinant aP2 stimulates glucose production and gluconeogenic activity in primary hepatocytes in vitro and in lean mice in vivo. In contrast, neutralization of secreted aP2 reduces glucose production and corrects the diabetic phenotype of obese mice. Hyperinsulinemic-euglycemic and pancreatic clamp studies upon aP2 administration or neutralization demonstrated actions of aP2 in liver. We conclude that aP2 is an adipokine linking adipocytes to hepatic glucose production and that neutralizing secreted aP2 may represent an effective therapeutic strategy against diabetes.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Cao H,Sekiya M,Ertunc ME,Burak MF,Mayers JR,White A,Inouye K,Rickey LM,Ercal BC,Furuhashi M,Tuncman G,Hotamisligil GSdoi
10.1016/j.cmet.2013.04.012subject
Has Abstractpub_date
2013-05-07 00:00:00pages
768-78issue
5eissn
1550-4131issn
1932-7420pii
S1550-4131(13)00155-1journal_volume
17pub_type
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