title: Increased insulin sensitivity and reduced adiposity in phosphatidylinositol 5-phosphate 4-kinase beta-/- mice.
abstract: Phosphorylated derivatives of the lipid phosphatidylinositol are known to play critical roles in insulin response. Phosphatidylinositol 5-phosphate 4-kinases convert phosphatidylinositol 5-phosphate to phosphatidylinositol 4,5-bis-phosphate. To understand the physiological role of these kinases, we generated mice that do not express phosphatidylinositol 5-phosphate 4-kinase beta. These mice are hypersensitive to insulin and have reduced body weights compared to wild-type littermates. While adult male mice lacking phosphatidylinositol 5-phosphate 4-kinase beta have significantly less body fat than wild-type littermates, female mice lacking phosphatidylinositol 5-phosphate 4-kinase beta have increased insulin sensitivity in the presence of normal adiposity. Furthermore, in vivo insulin-induced activation of the protein kinase Akt is enhanced in skeletal muscle and liver from mice lacking phosphatidylinositol 5-phosphate 4-kinase beta. These results indicate that phosphatidylinositol 5-phosphate 4-kinase beta plays a role in determining insulin sensitivity and adiposity in vivo and suggest that inhibitors of this enzyme may be useful in the treatment of type 2 diabetes.
authors.affiliation: Beth Israel Hospital, Harvard Institutes of Medicine, Division of Signal Transduction, 10th Floor, 330 Brookline, MA 02215, USA.
authors.forename: Katja A
authors.initials: KA
authors.lastname: Lamia
authors.forename: Odile D
authors.initials: OD
authors.lastname: Peroni
authors.forename: Young-Bum
authors.initials: YB
authors.lastname: Kim
authors.forename: Lucia E
authors.initials: LE
authors.lastname: Rameh
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Kahn
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Cantley
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D004435:Eating / Q000235:genetics / Q000502:physiology; D005260:Female; D007328:Insulin / Q000378:metabolism*; D020738:Leptin / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D020738:Leptin; D018129:Phosphatidylinositol Phosphates; C113567:phosphatidylinositol 5-phosphate; D010770:Phosphotransferases