Wild-type glycerol kinase of Escherichia coli is inhibited by both nonphosphorylated enzyme IIIGlc of the phosphoenolpyruvate:carbohydrate phosphotransferase system and fructose 1,6-diphosphate. Mutant glycerol kinase, resistant to inhibition by fructose 1,6-diphosphate, was much less sensitive to inhibition by enzyme IIIGlc. The difference between the wild-type and mutant enzymes was even grea...

GLUCOKINASE (GK) is the enzyme that converts glucose, a major fuel of the body, into glucose-6-phosphate (G-6-P) in liver, pancreatic beta cells, and some specialized neurons, as well as enteroendocrine and pituitary cells (12). G-6-P is the gateway to the major pathways of glucose utilization: glycolysis, the oxidation of glucose, the pentose phosphate pathway, and glycogenesis. GK performs di...

The molecular pathways leading to islet fibrosis in diabetes are unknown. Therefore, we studied gene expression in islets of 4-month-old Goto-Kakizaki (GK) and Wistar control rats. Of 71 genes found to be overexpressed in GK islets, 24% belong to extracellular matrix (ECM)/cell adhesion and 34% to inflammatory/immune response families. Based on gene data, we selected several antibodies to study...

We investigated the effect of diabetic plasma on insulin-stimulated DNA synthesis in primary cultured aortic smooth muscle cells (SMC) of the GK rat, a model of non-insulin-dependent diabetes mellitus, and compared it with that of Wistar normal rat plasma. We measured the incorporation of 3H-thymidine into cultured SMC. The diabetic plasma (3%) of GK rat, but neither the plasma (3%) of Wistar n...

AIM Type 2 diabetes is associated with stroke and cardiac dysfunction. We therefore investigated isolated middle cerebral arteries and coronary septal arteries from the diabetic Goto-Kakizaki (GK) rat model of nonobese type 2 diabetes. METHODS Myogenic tone and agonist-induced responses were investigated under isobaric conditions with simultaneous recording of [Ca2+]i. Rho-kinase and NO pathw...

Post-translational protein modifications such as acetylation have significant regulatory roles in metabolic processes, but their relationship to both variation in gene expression and DNA sequence is unclear. We address this question in the Goto-Kakizaki (GK) rat inbred strain, a model of polygenic type 2 diabetes. Expression of the NAD-dependent deacetylase Sirtuin-3 is down-regulated in GK rat...

Protein kinase C (PKC) is a family of protein kinases controlling protein phosphorylation and playing important roles in the regulation of metabolism. We have investigated expression levels of PKC isoforms in pancreatic islets and liver of diabetic Goto-Kakizaki (GK) rats with and without insulin treatment to evaluate their association with glucose homeostasis. mRNA and protein expression level...

Glucokinase (GK) is a monomeric allosteric enzyme and plays a pivotal role in blood glucose homeostasis. GK is regulated by GK regulatory protein (GKRP), and indirectly by allosteric effectors of GKRP. Despite the critical roles of GK and GKRP, the molecular basis for the allosteric regulation mechanism of GK by GKRP remains unclear. We determined the crystal structure of Xenopus GK and GKRP co...

Logic of knowledge and justified assumptions, also known as logic of grounded knowledge (GK), was proposed by Lin and Shoham as a general logic for nonmonotonic reasoning. To date, it has been used to embed in it default logic, autoepistemic logic, and general logic programming under stable model semantics. Besides showing the generality of GK as a logic for nonmonotonic reasoning, these embedd...