Investigation of the mechanism by which glucose analogues cause translocation of glucokinase in hepatocytes: evidence for two glucose binding sites.

  title={Investigation of the mechanism by which glucose analogues cause translocation of glucokinase in hepatocytes: evidence for two glucose binding sites.},
  author={Loranne Agius and Mark Stubbs},
  journal={The Biochemical journal},
  volume={346 Pt 2},
Glucokinase translocates between the cytoplasm and nucleus of hepatocytes where it is bound to a 68 kDa protein. The mechanism by which glucose induces translocation of glucokinase from the nucleus was investigated using glucose analogues that are not phosphorylated by glucokinase. There was strong synergism on glucokinase translocation between effects of glucose analogues (glucosamine, 5-thioglucose, mannoheptulose) and sorbitol, a precursor of fructose 1-phosphate. In the absence of glucose… Expand
Glucose 6-phosphate causes translocation of phosphorylase in hepatocytes and inactivates the enzyme synergistically with glucose.
Glucose 6-P causes both translocation of phosphorylase and inactivation, indicating a more complex role in the regulation of glycogen metabolism than can be explained from regulation of glyogen synthase alone. Expand
Analysis of the Cooperativity of Human β-Cell Glucokinase through the Stimulatory Effect of Glucose on Fructose Phosphorylation*
It is shown by computer simulation that a model can account for the kinetic properties of glucokinase, including the differential ability of mannoheptulose and N-acetylglucosamine to suppress cooperativity, and support models involving the existence of two slowly interconverting conformations of glucose that differ through their affinity for glucose and for glucose analogs. Expand
Inhibition of glucokinase translocation by AMP-activated protein kinase is associated with phosphorylation of both GKRP and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.
  • M. Mukhtar, V. A. Payne, +4 authors L. Agius
  • Chemistry, Medicine
  • American journal of physiology. Regulatory, integrative and comparative physiology
  • 2008
The rate of glucose phosphorylation in hepatocytes is determined by the subcellular location of glucokinase and by its association with its regulatory protein (GKRP) in the nucleus. Elevated glucoseExpand
Subcellular localization, mobility, and kinetic activity of glucokinase in glucose-responsive insulin-secreting cells.
It is concluded that glucokinase is present in two locations, cytoplasm and the granular compartment, and that it does not translocate between them, consistent with the lack of adaptive changes in the glucose phosphorylation affinity. Expand
Dual role of phosphofructokinase-2/fructose bisphosphatase-2 in regulating the compartmentation and expression of glucokinase in hepatocytes.
It is concluded that PFK2 has a dual role in regulating glucokinase in hepatocytes: it potentiates glucokin enzyme protein expression by posttranscriptional mechanisms and favors its cytoplasmic compartmentation. Expand
Glucokinase and molecular aspects of liver glycogen metabolism.
  • L. Agius
  • Biology, Medicine
  • 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. Expand
Stimulation of hepatocyte glucose metabolism by novel small molecule glucokinase activators.
GK activators are potential antihyperglycemic agents for the treatment of type 2 diabetes through the stimulation of hepatic glucose metabolism by a mechanism independent of GKRP. Expand
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 ofExpand
Glucokinase is an integral component of the insulin granules in glucose-responsive insulin secretory cells and does not translocate during glucose stimulation.
The results suggest that glucokinase is an integral component of the granule and does not translocate during glucose stimulation and is implicated in granule fusion. Expand
A defect in glucose-induced dissociation of glucokinase from the regulatory protein in Zucker diabetic fatty rats in the early stage of diabetes.
The decreased glucose effectiveness to suppress EGP and stimulate hepatic glucose uptake may result from failure of the sugar to activate GK by stimulating the translocation of the enzyme. Expand