PID1 in adipocytes modulates whole-body glucose homeostasis
Autor: | Lei Yang, Ling Chen, Xing Wang, Xianwei Cui, Lingxia Pang, Xingyun Wang, Yahui Zhou, Chunmei Shi, Lianghui You, Yao Gao, Jingai Zhu, Xirong Guo, Fangyan Huang, Chenbo Ji |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Adipose Tissue White Glucose uptake medicine.medical_treatment Biophysics Mice Transgenic Carbohydrate metabolism Fatty Acid-Binding Proteins Biochemistry Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Insulin resistance Structural Biology 3T3-L1 Cells Internal medicine Adipocytes Genetics medicine Animals Homeostasis Humans Insulin Glucose homeostasis Molecular Biology Protein kinase B Mice Knockout Glucose Transporter Type 4 biology Chemistry Tumor Suppressor Proteins medicine.disease Insulin receptor Glucose 030104 developmental biology Endocrinology Receptors LDL 030220 oncology & carcinogenesis biology.protein Insulin Resistance Carrier Proteins Low Density Lipoprotein Receptor-Related Protein-1 GLUT4 Protein Binding |
Zdroj: | Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1861:125-132 |
ISSN: | 1874-9399 |
Popis: | The novel obesity-associated protein Phosphotyrosine Interaction Domain containing 1 (PID1) inhibits insulin-PI3K/Akt signaling pathway and insulin-stimulated glucose uptake in vitro. In this study, we generated fat tissue-specific aP2-PID1 transgenic (aP2-PID1tg) mice and PID1 knockout (PID1-/-) mice to explore how PID1 affects glucose metabolism in vivo. We observed insulin resistance and impaired insulin-PI3K/Akt signaling in aP2-PID1tg mice. Consistent with these data, the PID1-/- mice displayed improved glucose tolerance and insulin sensitivity under chow diet, with increased Akt phosphorylation in white adipose tissue (WAT). We further demonstrated that PID1 could interact with low density lipoprotein receptor-related protein 1 (LRP1) but not the insulin receptor (IR) in adipocytes, and its overexpression could lead to decreased GLUT4 level. Our results thus indentify PID1 as a critical regulator of glucose metabolism in adipocytes. |
Databáze: | OpenAIRE |
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