TRB3: A tribbles Homolog That Inhibits Akt/PKB Activation by Insulin in Liver

@article{Du2003TRB3AT,
  title={TRB3: A tribbles Homolog That Inhibits Akt/PKB Activation by Insulin in Liver},
  author={Keyong Du and Stephan Herzig and Rohit N. Kulkarni and Marc Montminy},
  journal={Science},
  year={2003},
  volume={300},
  pages={1574 - 1577}
}
Insulin resistance is a major hallmark in the development of type II diabetes, which is characterized by the failure of insulin to promote glucose uptake in muscle and to suppress glucose production in liver. The serine-threonine kinase Akt (PKB) is a principal target of insulin signaling that inhibits hepatic glucose output when glucose is available from food. Here we show that TRB3, a mammalian homolog of Drosophila tribbles, functions as a negative modulator of Akt. TRB3 expression is… 
Hepatic Phosphoserine Aminotransferase 1 Regulates Insulin Sensitivity in Mice via Tribbles Homolog 3
TLDR
It is found that serine mediates PSAT1 regulation of TRB3 expression and insulin signaling in vitro and in vivo, and this results suggest that nonessential amino acid serine may play an important role in regulating insulin sensitivity.
Aberrant hepatic TRIB3 gene expression in insulin-resistant obese humans
TLDR
Evidence is found for a role of aberrant hepatic TRIB3 transcript levels in insulin resistance in obese humans and potential transcriptional pathways involved in regulation of TRIB 3 gene expression in the liver are identified.
Genetic Deletion of Trb3, the Mammalian Drosophila tribbles Homolog, Displays Normal Hepatic Insulin Signaling and Glucose Homeostasis
TLDR
Deletion of Trib3 has minimal effect on insulin-induced Akt activation in hepatic tissue, and, as such, any nonredundant role for Trb3 in the maintenance of glucose and energy homeostasis in mice is questioned.
The pseudokinase tribbles homolog 3 interacts with ATF4 to negatively regulate insulin exocytosis in human and mouse beta cells.
TLDR
Data link a missense polymorphism in human TRB3 to impaired insulin exocytosis and thus increased risk for T2DM.
Skeletal Muscle-Selective Knockout of LKB1 Increases Insulin Sensitivity, Improves Glucose Homeostasis, and Decreases TRB3
TLDR
It is found that a lack of LKB1 in skeletal muscle enhanced insulin sensitivity, as evidenced by decreased fasting glucose and insulin concentrations, improved glucose tolerance, increased muscle glucose uptake in vivo, and increased glucose utilization during a hyperinsulinemic-euglycemic clamp.
The role of TRIB3 in insulin resistance: Its action as nutrient sensor and regulator of insulin signal action
TLDR
It is found that hyperglycemia induces increments in TRIB3 expression partially through glucose metabolism via the hexosamine biosynthesis pathway, and data for the first time indicate that TRIB 3 can contribute to glucose-induced insulin resistance.
Effect of TRB3 on Insulin and Nutrient-stimulated Hepatic p70 S6 Kinase Activity*
TLDR
The results suggest that the nutrient excess in the hyperphagic, hyperinsulinemic db/db mouse primes the hepatocyte to respond to nutrients resulting in elevated S6K1 activity and decreased insulin signaling via the IRS-1/phosphatidylinositol 3-kinase/Akt pathway.
Signalling: A sugar fix for fasters
  • K. Bussell
  • Chemistry
    Nature Reviews Molecular Cell Biology
  • 2003
Normally, insulin binding to its receptor induces phosphorylation of the serine/threonine kinase Akt/protein kinase B (PKB). One of Akt/PKB’s functions is to inhibit glucose output from the liver
Identification of the tyrosine phosphatase PTP-MEG2 as an antagonist of hepatic insulin signaling.
TLDR
Data implicate PTP-MEG2 as a mediator of blood glucose homeostasis through antagonism of insulin signaling, and suggest that modulation of PTCG2 activity may be an effective strategy in the treatment of type 2 diabetes.
PGC-1 promotes insulin resistance in liver through PPAR-α-dependent induction of TRB-3
TLDR
It is shown that, in the liver, TRB-3 is a target for PPAR-α, a fasting-inducible inhibitor of the serine-threonine kinase Akt/PKB, which indicates a link between nuclear hormone receptor and insulin signaling pathways, and suggest a potential role for TRb-3 inhibitors in the treatment of type 2 diabetes.
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