Increased insulin sensitivity and reduced adiposity in phosphatidylinositol 5-phosphate 4-kinase beta-/- mice.
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.
Lamia
Katja A
KA
Beth Israel Hospital, Harvard Institutes of Medicine, Division of Signal Transduction, 10th Floor, 330 Brookline, MA 02215, USA.
Peroni
Odile D
OD
Kim
Young-Bum
YB
Rameh
Lucia E
LE
Kahn
Barbara B
BB
Cantley
Lewis C
LC
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*
D007328:Insulin; D020738:Leptin; D018129:Phosphatidylinositol Phosphates; C113567:phosphatidylinositol 5-phosphate; D010770:Phosphotransferases