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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., Kang, M.C., Yang, W.M., Hwang, W.M., Kim, S.S., Hong, S.H., Heo, J.I., Vijyakumar, A., Pereira de Moura, L., Uner, A., Huang, H., Lee, S.H., Lima, I.S., Park, K.S., Kim, M.S., Dagon, Y., Willnow, T.E., Aroda, V., Ciaraldi, T.P., 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 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 11 |
| Number: | 1 |
| 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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