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The association of phosphoinositide 3‐kinase enhancer A with hepatic insulin receptor enhances its kinase activity
Author(s) -
Chan Chi Bun,
Liu Xia,
He Kunyan,
Qi Qi,
Jung Dae Y,
Kim Jason K,
Ye Keqiang
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2011.108
Subject(s) - insulin receptor , phosphoinositide 3 kinase , endocrinology , medicine , insulin , protein kinase b , glucose homeostasis , biology , tyrosine kinase , signal transduction , insulin resistance , microbiology and biotechnology
Dysfunction of hepatic insulin receptor tyrosine kinase (IRTK) causes the development of type 2 diabetes. However, the molecular mechanism regulating IRTK activity in the liver remains poorly understood. Here, we show that phosphoinositide 3‐kinase enhancer A (PIKE‐A) is a new insulin‐dependent enhancer of hepatic IRTK. Liver‐specific Pike ‐knockout (LPKO) mice display glucose intolerance with impaired hepatic insulin sensitivity. Specifically, insulin‐provoked phosphoinositide 3‐kinase/Akt signalling is diminished in the liver of LPKO mice, leading to the failure of insulin‐suppressed gluconeogenesis and hyperglycaemia. Thus, hepatic PIKE‐A has a key role in mediating insulin signal transduction and regulating glucose homeostasis in the liver.