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

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Item Type:Article
Title:Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity
Creators Name:Seo, J.A. and Kang, M.C. and Yang, W.M. and Hwang, W.M. and Kim, S.S. and Hong, S.H. and Heo, J.I. and Vijyakumar, A. and Pereira de Moura, L. and Uner, A. and Huang, H. and Lee, S.H. and Lima, I.S. and Park, K.S. and Kim, M.S. and Dagon, Y. and Willnow, T.E. and Aroda, V. and Ciaraldi, T.P. and Henry, R.R. and Kim, Y.B.
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.
Keywords:Animal Disease Models, Cell Line, Clusterin, Glucose, Glucose Clamp Technique, Hypoglycemic Agents, Insulin, Insulin Receptor, Insulin Resistance, Knockout Mice, Liver, Low Density Lipoprotein Receptor-Related Protein-2, Pioglitazone, Polycystic Ovary Syndrome, Signal Transduction, Skeletal Muscle, Animals, Mice
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:2024
Date:24 April 2020
Additional Information:Erratum in: Nat Commun 11: 2276.
Official Publication:https://doi.org/10.1038/s41467-020-15963-w
PubMed:View item in PubMed

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