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Adipocyte lipid chaperone AP2 is a secreted adipokine regulating hepatic glucose production. | LitMetric

AI Article Synopsis

  • Proper regulation of hepatic glucose production is crucial for maintaining overall glucose balance in the body, and disruptions in this process are significant in diabetes.
  • The protein aP2, known for its role as an intracellular lipid chaperone, is secreted by adipose tissue to influence liver glucose metabolism, with higher levels found in obesity.
  • Administering aP2 increases glucose production in liver cells, while neutralizing it can lower glucose levels and improve diabetic symptoms in obese mice, suggesting aP2 could be a target for diabetes treatment.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755450PMC
http://dx.doi.org/10.1016/j.cmet.2013.04.012DOI Listing

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