Inositol Pyrophosphates Inhibit Akt Signaling, Thereby Regulating Insulin Sensitivity and Weight Gain

Cited 272 time in webofscience Cited 0 time in scopus
  • Hit : 391
  • Download : 0
The inositol pyrophosphate IP7 (5-diphosphoinositolpentakisphosphate), formed by a family of three inositol hexakisphosphate kinases (IP6Ks), modulates diverse cellular activities. We now report that IP7 is a physiologic inhibitor of Akt, a serine/threonine kinase that regulates glucose homeostasis and protein translation, respectively, via the GSK3 beta and mTOR pathways. Thus, Akt and mTOR signaling are dramatically augmented and GSK3b signaling reduced in skeletal muscle, white adipose tissue, and liver of mice with targeted deletion of IP6K1. IP7 affects this pathway by potently inhibiting the PDK1 phosphorylation of Akt, preventing its activation and thereby affecting insulin signaling. IP6K1 knockout mice manifest insulin sensitivity and are resistant to obesity elicited by high-fat diet or aging. Inhibition of IP6K1 may afford a therapeutic approach to obesity and diabetes.
Publisher
CELL PRESS
Issue Date
2010-12
Language
English
Article Type
Article
Keywords

PROTEIN-KINASE-B; DIET-INDUCED OBESITY; MICE LACKING; TELOMERE LENGTH; SKELETAL-MUSCLE; PPAR-GAMMA; FAT MASS; RESISTANCE; PHOSPHORYLATION; HEXAKISPHOSPHATE

Citation

CELL, v.143, no.6, pp.897 - 910

ISSN
0092-8674
DOI
10.1016/j.cell.2010.11.032
URI
http://hdl.handle.net/10203/99349
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 272 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0