Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance

@article{Yang2008PhosphoinositideSL,
  title={Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance},
  author={Xiaoyong Yang and Pat P. Ongusaha and Philip D.G. Miles and Joyce C. Havstad and Fengxue Zhang and W. Venus So and Jeffrey E. Kudlow and Robert H. Michell and Jerrold M. Olefsky and Seth J. Field and Ronald M. Evans},
  journal={Nature},
  year={2008},
  volume={451},
  pages={964-969}
}
Glucose flux through the hexosamine biosynthetic pathway leads to the post-translational modification of cytoplasmic and nuclear proteins by O-linked β-N-acetylglucosamine (O-GlcNAc. [] Key Result After induction with insulin, phosphatidylinositol 3,4,5-trisphosphate recruits OGT from the nucleus to the plasma membrane, where the enzyme catalyses dynamic modification of the insulin signalling pathway by O-GlcNAc.
O-GlcNAc modification, insulin signaling and diabetic complications.
Cross-talk between GlcNAcylation and phosphorylation: roles in insulin resistance and glucose toxicity.
TLDR
Recent technical advances in O-GlcNAc site-mapping methods should now finally allow for a much-needed increase in site-specific analyses to address the functional significance of O- GlcNAcylation in insulin resistance and glucose toxicity as well as other major biological processes.
Regulation of Akt signaling by O-GlcNAc in euglycemia.
TLDR
It is found that overexpression of O-GlcNAcase in the livers of euglycemic mice also significantly increased Akt activity, resulting in increased phosphorylation of downstream targets and decreased mRNA for glucose-6-phosphatase and phosphoenolpyruvate carboxykinase.
[Protein O-GlcNAcylation and regulation of cell signalling: involvement in pathophysiology].
TLDR
O-GlcNAcylation appears to be a major regulator of cellular activities and may play an important part in different human diseases, however, because of the large spectrum of OGT and OGA substrates, targeting O-Gl cnacylation for treatment of these diseases will be a highly challenging task.
Regulation of the O-Linked β-N-Acetylglucosamine Transferase by Insulin Signaling*
TLDR
It is shown that OGT is activated by insulin signaling, a well characterized insulin receptor substrate, and it is concluded that insulin stimulates the tyrosine phosphorylation and activity of OGT.
Real Talk: The Inter-play Between the mTOR, AMPK, and Hexosamine Biosynthetic Pathways in Cell Signaling
TLDR
Research into the individual nutrient-sensitivities of the HBP, AMPK, and mTOR pathways has revealed a complex regulatory dynamic, where their unique responses to macromolecule levels coordinate cell behavior.
Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease.
TLDR
Recent glycomic analyses have shown that O-GlcNAcylation has surprisingly extensive cross talk with phosphorylation, where it serves as a nutrient/stress sensor to modulate signaling, transcription, and cytoskeletal functions.
Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis
TLDR
The regulation of these processes by O-GlcNAc and the impact of such regulation on survival in models of ischemia reperfusion injury and trauma hemorrhage are discussed.
New Insights into Metabolic Signaling and Cell Survival: The Role of β-O-Linkage of N-Acetylglucosamine
TLDR
Recent insights into O-GlcNAc signaling in the cardiovascular system as a paradigm for its involvement in other biological systems are addressed.
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References

SHOWING 1-10 OF 63 REFERENCES
The Hexosamine Signaling Pathway: Deciphering the "O-GlcNAc Code"
TLDR
This review will begin to answer how the enzymes of O-GlcNAc cycling are regulated and how the cycle may interface with other cellular signaling pathways.
Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes
TLDR
Elevation of O-GlcNAc levels attenuate insulin signaling and contribute to the mechanism by which increased flux through the HSP leads to insulin resistance in adipocytes.
Hexosamines, insulin resistance, and the complications of diabetes: current status.
  • M. Buse
  • Biology
    American journal of physiology. Endocrinology and metabolism
  • 2006
TLDR
Increased flux through HBP is required and sufficient for some of the metabolic effects of sustained, increased glucose flux, which promotes the complications of diabetes, e.g., diminished expression of sarcoplasmic reticulum Ca(2+)-ATPase in cardiomyocytes and induction of TGF-beta and plasminogen activator inhibitor-1 in vascular smooth muscle cells, mesangial cells, and aortic endothelial cells.
O-GlcNAc modification on IRS-1 and Akt2 by PUGNAc inhibits their phosphorylation and induces insulin resistance in rat primary adipocytes
TLDR
The results suggest that the increase of O-GlcNAc modification on insulin signal pathway intermediates, such as IRS-1 and Akt2, reduces the insulin-stimulated phosphorylation of IRS- 1 and AkT2, subsequently leading to insulin resistance in rat primary adipocytes.
Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling.
TLDR
Using mechanisms such as this, PI 3-kinase is able to act as a molecular switch to regulate the activity of serine/threonine-specific kinase cascades important in mediating insulin's effects on endpoint responses.
O-linkage of N-acetylglucosamine to Sp1 activation domain inhibits its transcriptional capability
TLDR
It is shown that O-GlcNAcylation of a chimeric transcriptional activator containing the second activation domain of Sp1 decreases its transcriptional activity both in an in vitro transcription system and in living cells, which is in concert with the observation that O -Glc NAcylationof Sp1 activation domain blocks its in vitro and in vivo interactions with other Sp1 molecules and TATA-binding protein-associated factor II 110.
The role of O-linked protein glycosylation in β-cell dysfunction (review)
TLDR
A model is developed suggesting how beta-cell O-glycosylation is also involved in the development and progression of type 2 diabetes in humans.
Glucose stimulates protein modification by O-linked GlcNAc in pancreatic β cells: Linkage of O-linked GlcNAc to β cell death
TLDR
A causal link between apoptosis in β cells and glucose metabolism through glucosamine to O-GlcNAc is provided, implicating this pathway of glucose metabolism with β cell glucose toxicity.
The role of O-linked protein glycosylation in beta-cell dysfunction.
TLDR
A model is developed suggesting how beta-cell O-glycosylation is also involved in the development and progression of type 2 diabetes in humans.
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