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
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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