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

Autor: Seo JA; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; Division of Endocrinology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Kang MC; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; Research Group of Food Processing, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Korea., Yang WM; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea., Hwang WM; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; Division of Nephrology, Department of Internal Medicine, College of Medicine, Konyang University, Daejeon, Korea., Kim SS; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; Department of Internal Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea., Hong SH; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; Columbia University, New York, NY, USA., Heo JI; Division of Endocrinology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea., Vijyakumar A; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA., Pereira de Moura L; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; School of Applied Science, University of Campinas, Limeira, Brazil., Uner A; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA., Huang H; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; East Carolina University, East Carolina Diabetes and Obesity Institute, Greenville, NC, USA., Lee SH; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; College of Medicine, The Catholic University of Korea, Seoul, Korea., Lima IS; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; Universidade Nova de Lisboa, Lisboa, Portugal., Park KS; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea., Kim MS; Department of Internal Medicine, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea., Dagon Y; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA., Willnow TE; Molecular Cardiovascular Research, Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany., Aroda V; Veterans Affairs San Diego Healthcare System (9111 G), San Diego, CA, 92161, USA.; Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.; Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Ciaraldi TP; Veterans Affairs San Diego Healthcare System (9111 G), San Diego, CA, 92161, USA.; Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA., Henry RR; Veterans Affairs San Diego Healthcare System (9111 G), San Diego, CA, 92161, USA.; Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA., Kim YB; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. ykim2@bidmc.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 Apr 24; Vol. 11 (1), pp. 2024. Date of Electronic Publication: 2020 Apr 24.
DOI: 10.1038/s41467-020-15963-w
Abstrakt: 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.
Databáze: MEDLINE