title: The association of phosphoinositide 3-kinase enhancer A with hepatic insulin receptor enhances its kinase activity.
abstract: 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.
authors: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, Georgia 30322, USA.
authors: Chi Bun
authors: CB
authors: Chan
authors: Xia
authors: X
authors: Liu
authors: Kunyan
authors: K
authors: He
authors: Qi
authors: Q
authors: Qi
authors: Dae Y
authors: DY
authors: Jung
authors: Jason K
authors: JK
authors: Kim
authors: Keqiang
authors: K
authors: Ye
mesh_terms: D000818:Animals; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D005943:Gluconeogenesis / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007328:Insulin; D009419:Nerve Tissue Proteins; C410467:insulin receptor tyrosine kinase; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D020558:GTP Phosphohydrolases; C529781:PIKE protein, mouse; D005947:Glucose