PID1 in adipocytes modulates whole-body glucose homeostasis

Ling Chen; Xing-Yun Wang; Jin-Gai Zhu; Liang-Hui You; Xing Wang; Xian-Wei Cui; Chun-Mei Shi; Fang-Yan Huang; Ya-Hui Zhou; Lei Yang; Ling-Xia Pang; Yao Gao; Chen-Bo Ji; Xi-Rong Guo

doi:10.1016/j.bbagrm.2018.01.001

PID1 in adipocytes modulates whole-body glucose homeostasis

Biochim Biophys Acta Gene Regul Mech. 2018 Feb;1861(2):125-132. doi: 10.1016/j.bbagrm.2018.01.001. Epub 2018 Jan 31.

Authors

Affiliations

¹ Nanjing Maternal and Child Health Hospital, Nanjing 210004, China; Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China.
² Nanjing Maternal and Child Health Hospital, Nanjing 210004, China; Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China. Electronic address: chenboji@njmu.edu.cn.
³ Nanjing Maternal and Child Health Hospital, Nanjing 210004, China; Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China. Electronic address: xrguo@njmu.edu.cn.

PMID: 29391195
DOI: 10.1016/j.bbagrm.2018.01.001

Abstract

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-PID1^tg) 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-PID1^tg 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.

Keywords: GLUT4; Insulin resistance; LRP1; PID1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3-L1 Cells
Adipocytes / metabolism*
Adipose Tissue, White / metabolism
Animals
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Fatty Acid-Binding Proteins / genetics
Fatty Acid-Binding Proteins / metabolism
Glucose / metabolism*
Glucose Transporter Type 4 / metabolism
Homeostasis*
Humans
Insulin / metabolism
Insulin Resistance
Low Density Lipoprotein Receptor-Related Protein-1
Mice
Mice, Knockout
Mice, Transgenic
Phosphatidylinositol 3-Kinases / metabolism
Protein Binding
Receptors, LDL / metabolism
Tumor Suppressor Proteins / metabolism

Substances

Carrier Proteins
Fabp4 protein, mouse
Fatty Acid-Binding Proteins
Glucose Transporter Type 4
Insulin
Low Density Lipoprotein Receptor-Related Protein-1
Lrp1 protein, mouse
NYGGF4 protein, mouse
Receptors, LDL
Slc2a4 protein, mouse
Tumor Suppressor Proteins
Glucose