Increased insulin sensitivity and hypoglycaemia in mice lacking the p85α subunit of phosphoinositide 3–kinase

摘要: The hallmark of type 2 diabetes, the most common metabolic disorder, is a defect in insulin-stimulated glucose transport peripheral tissues. Although role for phosphoinositide-3-kinase (PI3K) activity and transporter isoform 4 (Glut4) translocation has been suggested vitro, its vivo molecular link between activation PI3K not yet elucidated. To determine homeostasis, we generated mice with targeted disruption gene encoding p85alpha regulatory subunit (Pik3r1; refs 3-5). Pik3r1-/- showed increased insulin sensitivity hypoglycaemia due to skeletal muscle adipocytes. Insulin-stimulated associated receptor substrates (IRSs) was mediated via full-length p85 alpha wild-type mice, but p50 alternative splicing same mice. This switch an increase insulin-induced generation phosphatidylinositol(3,4,5)triphosphate (PtdIns(3,4,5)P3) adipocytes facilitation Glut4 from low-density microsome (LDM) fraction plasma membrane (PM). mechanism seems be responsible phenotype namely hypoglycaemia. Our work provides first direct evidence that have homeostasis vivo.