共 36 条
Increased insulin sensitivity and reduced adiposity in phosphatidylinositol 5-phosphate 4-kinase β-/- mice
被引:92
作者:

Lamia, KA
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机构: Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA

Peroni, OD
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h-index: 0
机构: Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA

Kim, YB
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h-index: 0
机构: Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA

Rameh, LE
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h-index: 0
机构: Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA

Kahn, BB
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h-index: 0
机构: Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA

Cantley, LC
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机构: Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA
机构:
[1] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
[3] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA USA
[4] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[5] Boston Biomed Res Inst, Watertown, MA USA
关键词:
D O I:
10.1128/MCB.24.11.5080-5087.2004
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Phosphorylated derivatives of the lipid phosphatidylinositoll are known to play critical roles in insulin response. Phosphatidylinositol 5-phosphate 4-kinases convert phosphatidlylinositol 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 mate 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 phosphatidlylinositol 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.
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页码:5080 / 5087
页数:8
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