Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity
| Autor: | Theodore P. Ciaraldi, Inês S. Lima, Yossi Dagon, Ji A Seo, Achana Vijyakumar, Jee In Heo, Vanita R. Aroda, Robert R. Henry, Hu Huang, Min-Cheol Kang, Won Mo Yang, Kyong Soo Park, Aykut Göktürk Üner, Soo Hong, Won Min Hwang, Sang Soo Kim, Leandro Pereira de Moura, Min Seon Kim, Thomas E. Willnow, Seung-Hwan Lee, Young-Bum Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_treatment Glucose uptake General Physics and Astronomy Mice 0302 clinical medicine Insulin Glucose homeostasis lcsh:Science Mice Knockout Multidisciplinary biology Chemistry Endocrine system and metabolic diseases Polycystic ovary Low Density Lipoprotein Receptor-Related Protein-2 medicine.anatomical_structure Liver Female Polycystic Ovary Syndrome Signal Transduction Adult medicine.medical_specialty Science 030209 endocrinology & metabolism Carbohydrate metabolism General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences Insulin resistance Internal medicine medicine Animals Humans Hypoglycemic Agents Muscle Skeletal Author Correction Pioglitazone Skeletal muscle General Chemistry medicine.disease Receptor Insulin Disease Models Animal Insulin receptor Clusterin Glucose Metabolism 030104 developmental biology Endocrinology Cardiovascular and Metabolic Diseases Glucose Clamp Technique biology.protein lcsh:Q Insulin Resistance |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-15963-w |
| Popis: | 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: | OpenAIRE |
| Externí odkaz: |
|