Glucokinase (hexokinase IV) has a major role in the control of blood glucose homeostasis because it is the predominant hexokinase expressed in the liver, has a very high control strength on hepatic glucose disposal (1), and is the glucose sensor for insulin secretion in pancreatic -cells (2). Glucokinase is currently considered a strong candidate target for antihyperglycemic drugs for type 2 di...

The association of glucokinase with liver mitochondria has been reported [Danial et al. (2003) BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 424, 952-956]. We confirmed association of glucokinase immunoreactivity with rat liver mitochondria using Percoll gradient centrifugation and demonstrated its association with the 68 kDa regulatory p...

Glucose is an essential nutrient that must be distributed throughout the body to provide energy to sustain physiological functions. Glucose is delivered to distant tissues via be blood stream, and complex systems have evolved to maintain the levels of glucose within a narrow physiological range. Phosphorylation of glucose, by glucokinase, is an essential component of glucose homeostasis, both f...

The ubiquitin-proteasome system is important to maintain pancreatic β-cell function. Inhibition of the proteasome significantly reduced glucose-induced insulin secretion. Key regulators of the stimulus/secretion cascade seem to be affected by protein misfolding if the proteasome is down-regulated as recently reported in humans with Type 2 diabetes. It remains unknown, however, whether the gluco...

Glucose is the primary fuel for the brain. It has been proposed that the brain senses glucose, and promotes eating behaviours when levels are low. A system regulating glucose intake, driven by hedonic responses generated in the limbic system, has been identified. A taste-independent mechanism within the CNS that promotes glucose intake has been postulated. Glucokinase is a member of the hexokin...

Glucokinase activity is a major determinant of hepatic glucose metabolism and blood glucose homeostasis. Liver glucokinase activity is regulated acutely by adaptive translocation between the nucleus and the cytoplasm through binding and dissociation from its regulatory protein (GKRP) in the nucleus. Whilst the effect of glucose on this mechanism is well established, the role of hormones in regu...

OBJECTIVE Heterozygous activating mutations of glucokinase have been reported to cause hypoglycemia attributable to hyperinsulinism in a limited number of families. We report three children with de novo glucokinase hyperinsulinism mutations who displayed a spectrum of clinical phenotypes corresponding to marked differences in enzyme kinetics. RESEARCH DESIGN AND METHODS Mutations were directl...

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 glucose concentrations and precursors of fructose 1-phosphate (e.g., sorbitol) cause dissociation of glucokinase from GKRP and translocation to the cytoplasm. In this study, we investigated the counter-regu...

Glucokinase (GK) is a hexokinase isozyme that catalyzes the phosphorylation of glucose to glucose-6-phosphate. Glucokinase activators are being investigated as potential diabetes therapies because of their effects on hepatic glucose output and/or insulin secretion. Here, we have examined the efficacy and mechanisms of action of a novel glucokinase activator, GKA23. In vitro, GKA23 increased the...