The release of glucokinase from digitonin-permeabilized hepatocytes shows different characteristics with respect to ionic strength and [MgCl2] from the release of other cytoplasmic enzymes. Release of glucokinase is most rapid at low ionic strength (300 mM sucrose, 3 mM Hepes) and is inhibited by increasing concentration of KCl [concn. giving half-maximal inhibition (I50) 25 mM] or Mg2+ (I50 0....

Glucokinase and phosphorylase both have a high control strength over hepatocyte glycogen metabolism and are potential therapeutic targets for type 2 diabetes. We tested whether combined phosphorylase inactivation and glucokinase activation is a more effective strategy for controlling hepatic glycogen metabolism than single-site targeting. Activation of glucokinase by enzyme overexpression combi...

A glucokinase qualitatively and quantitatively adequate as the first and limiting step in the synthesis of glycogen from glucose has been recently identified in the liver of the normal fed rat. In contrast with hexokinase, glucokinase activity was found to disappear in fasted and alloxan-diabetic animals (1). A characteristic shared by deprivation of food and diabetes is the marked decrease of ...

Model studies are presented which demonstrate that reactions proceeding by a random ternary-complex mechanism may exhibit most pronounced deviations from Michaelis-Menten kinetics even if the reaction is effectively ordered with respect to net reaction flow. In particular, the kinetic properties and reaction flow characteristics of glucokinase can be accounted for in such terms. It is concluded...

Conditional expression of the glucokinase regulatory protein in insulinoma cells, under control of the reverse tetracycline-dependent transactivator, was used to investigate whether expression of this protein de novo would alter the intracellular distribution of glucokinase. The regulatory protein, which was undetectable in the basal state, could be induced by doxycycline to levels comparable t...

Inhibitors of signalling pathways were used to dissect the mechanism of insulin action on expression of the gene encoding glucokinase in cultured rat hepatocytes. Wortmannin and LY 294002 completely prevented the insulin-induced increase in glucokinase mRNA seen in unhibited cells, indicating that the phosphoinositide 3-kinase module has a key role. A ligand inducible protein kinase B (PKB, als...

BACKGROUND Glucokinase plays important tissue-specific roles in human physiology, where it acts as a sensor of blood glucose levels in the pancreas, and a few other cells of the gut and brain, and as the rate-limiting step in glucose metabolism in the liver. Liver-specific expression is driven by one of the two tissue-specific promoters, and has an absolute requirement for insulin. The sequence...

Hepatic glucokinase (EC 2.7.1.2) is first detectable around the 16th day in the neonatal rat [ l-31. Precocious appearance of the enzyme is induced by intubation of glucose; the resulting activities are enhanced by prior treatment of the animals with triiodothyronine (T3) [4,5]. The factors that regulate synthesis of glucokinase in neonatal rat liver are complex [6] and it would be advantageous...

Song Z, Levin BE, Stevens W, Sladek CD. Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors. Am J Physiol Regul Integr Comp Physiol 306: R447–R456, 2014. First published January 29, 2014; doi:10.1152/ajpregu.00520.2013.— Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin i...