The role of glucose 6‐phosphate in the control of glycogen synthase

  title={The role of glucose 6‐phosphate in the control of glycogen synthase},
  author={Carlos Viijlar‐Palas{\'i} and Joan J. Guinovart},
  journal={The FASEB Journal},
  pages={544 - 558}
Elevated blood glucose concentrations result in increased intracellular levels of glucose 6‐phosphate in liver, skeletal muscle, and adipose tissue. In liver, blood glucose concentrations are the main factor in control of the synthesis of glycogen; insulin has only a potentiating effect. In skeletal muscle and adipocytes, glucose alone has little effect on the activity of glycogen synthase, the limiting enzyme in glycogen synthesis. However, insulin released as a result of elevated blood… 
The Role of Glucose Metabolites in the Activation and Translocation of Glycogen Synthase by Insulin in 3T3-L1 Adipocytes*
The results indicate that glucose metabolites have an impact on the regulation of glycogen synthase activation and localization by insulin.
Glucokinase and molecular aspects of liver glycogen metabolism.
  • L. Agius
  • Biology, Chemistry
    The Biochemical journal
  • 2008
Defects in both the activation of glucokinase and in the dephosphorylation of glycogen phosphorylase are potential contributing factors to the dysregulation of hepatic glucose metabolism in Type 2 diabetes.
Glucose 6-phosphate regulates hepatic glycogenolysis through inactivation of phosphorylase.
High glucose concentration suppresses hepatic glycogenolysis by allosteric inhibition and dephosphorylation (inactivation) of phosphorylase-a. The latter effect is attributed to a direct effect of
Increased phosphorylation of skeletal muscle glycogen synthase at NH2-terminal sites during physiological hyperinsulinemia in type 2 diabetes.
Analysis using phospho-specific antibodies revealed that insulin decreases phosphorylation of sites 3a + 3b in human muscle, and this was accompanied by activation of Akt and inhibition of glycogen synthase kinase-3alpha in type 2 diabetic subjects, and in type 1 diabetic subjects these effects of insulin were fully intact.
Glucose-6-Phosphate–Mediated Activation of Liver Glycogen Synthase Plays a Key Role in Hepatic Glycogen Synthesis
Data show that G6P-mediated activation of GYS2 plays a key role in controlling glycogen synthesis and hepatic glucose-G6P flux control and thus whole-body glucose homeostasis.
Liver Glycogen Synthase but Not the Muscle Isoform Differentiates between Glucose 6-Phosphate Produced by Glucokinase or Hexokinase*
Adenovirus-mediated gene transfer into FTO-2B cells, a rat hepatoma cell line, indicates the existence of at least two pools of Glc-6-P in the cell, one of them is accessible to both isoforms of GS and is replenished by the action of GK, whereas LGS is excluded from the cellular compartment where the glucose- 6-P produced by HK I is directed.
Expression of glucokinase in cultured human muscle cells confers insulin-independent and glucose concentration-dependent increases in glucose disposal and storage.
It is concluded that expression of glucokinase in cultured human muscle cells results in proportional increases in insulin-independent glucose disposal, and that muscle glucose storage and utilization becomes controlled in a glucose concentration-dependent manner in AdCMV-GKL-treated cells.
Organizing glucose disposal: emerging roles of the glycogen targeting subunits of protein phosphatase-1.
New insights into the structure, function, regulation, and metabolic effects of the glycogen-targeting subunits of PP1 are summarized and the possibility that these molecules could serve as therapeutic targets for lowering of blood glucose in diabetes is evaluated.
Glucose 6-Phosphate Produced by Gluconeogenesis and by Glucokinase Is Equally Effective in Activating Hepatic Glycogen Synthase*
It is hypothesized that Glc-6-P has a major role in glycogen metabolism not only by determining the activation state of GS but also by controlling its subcellular distribution in the hepatocyte.


Activation of glycogen synthase in rat adipocytes by insulin and glucose involves increased glucose transport and phosphorylation.
Effects of glucose on the activation and translocation of glycogen synthase in diabetic rat hepatocytes.
No difference was found between healthy and diabetic rats in the capacity of glycogen synthase to translocate to pellets in response to an increase in glucose 6-phosphate, but in diabetic hepatocytes, this sugar was able to activate the enzyme found in the fractions that could be pelleted.
Role of glucose 6-phosphate in the translocation of glycogen synthase in rat hepatocytes.
It is indicated that glucose 6-phosphate plays a role in the translocation of glycogen synthase in rat hepatocytes and Microcystin, which blocks the activation of glucose by glucose, but not the accumulation of glucose6-ph phosphate, did not affect the translocated of the enzyme.
In Vivo Regulation of Liver and Skeletal Muscle Glycogen Synthase Activity by Glucose and Insulin
It is confirmed that blood glucose concentration is the major short-term regulator of glycogen synthase activity in the liver but that insulin is of prime importance in skeletal muscle.
Glucose-induced glycogenesis in the liver involves the glucose-6-phosphate-dependent dephosphorylation of glycogen synthase.
It is concluded that glucose elicits hepatic synthase phosphatase activity both by removal of the inhibitor, phosphorylase a, and by generation of the stimulator, Glc-6-P.
Glucose 6‐phosphate plays a central role in the regulation of glycogen synthesis in a glycogen‐storing liver cell line
It was concluded that glycogen accumulation in C1I cells was due to stimulation of synthase and inhibition of phosphorylase by Glc6‐P and not activation/inactivation of the enzymes seems to play a predominant role in glycogen collection in this cell line.
Substrate specific activation by glucose 6-phosphate of the dephosphorylation of muscle glycogen synthase.