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PANDER binds to the liver cell membrane and inhibits insulin signaling in HepG2 cells
Author(s) -
Yang Jichun,
Wang Chunjiong,
Li Jing,
Burkhardt Brant R.,
Robert-Cooperman Claudia E.,
Wilson Camella,
Gao Zhiyong,
Wolf Bryan A.
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.08.008
Subject(s) - insulin receptor , insulin , insulin receptor substrate , irs2 , chemistry , receptor , cytokine , microbiology and biotechnology , medicine , endocrinology , biology , biochemistry , insulin resistance
PANDER is a cytokine co‐secreted with insulin from islet β‐cells. To date, the physiological function of PANDER remains largely unknown. Here we show that PANDER binds to the liver membrane by 125 I‐PANDER saturation and competitive binding assays. In HepG2 cells, pre‐treatment with PANDER ranging from 4 pM to 4 nM for 8 h resulted in a maximal inhibition of insulin‐stimulated activation of insulin receptor and insulin receptor substrate 1 by 52% and 63%, respectively. Moreover, PANDER treatment also reduced insulin‐stimulated PI3K and pAkt levels by 55% and 48%, respectively. In summary, we have identified the liver as a novel target for PANDER, and PANDER may be involved in the progression of diabetes by regulating hepatic insulin signaling pathways.