Glucokinase and Glycemic Diseases: From Basics to Novel Therapeutics
Franz M. Matschinsky, Mark A. Magnuson
Karger Medical and Scientific Publishers, 2004 - Medical - 406 pages
The glucose-phosphorylating enzyme glucokinase (also known as hexokinase IV) plays a preeminent role as a glucose sensor and regulatory metabolic enzyme. The implications of this central position of glucokinase for the understanding and treatment of diabetes mellitus are far reaching. This book addresses the molecular and human genetic, as well as the physiological-chemical and pharmacological aspects of the role glucokinase plays in glucose homeostasis and diseases of glucose metabolism, and how the enzyme serves as the drug target for the treatment of diabetes mellitus. The collection of assays by a team of internationally renowned authors includes basic science chapters dealing with the enzymology, structure and the kinetics of hexokinases, essays describing the biochemical genetics of glucokinase-linked hypo- and hyperglycemia syndromes, and papers that discuss the diverse roles of the enzyme in a variety of tissues. Finally, the book contains the latest information on the recently discovered class of weight drugs that activate glucokinase (i.e. glucokinase activators or GKAs). This volume is of great interest to basic and clinical diabetes researchers, geneticists, biochemists, physiologists and pharmacologists.
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Acad Sci USA allosteric alloxan beta cell beta-cell binding Biol Chem blood glucose cytoplasm diabetes mellitus enzyme flux fructose function gene expression genetic GK activity GK protein GKAs GKRP glucagon glucokinase activity glucokinase gene glucokinase mRNA glucokinase mutations glucokinase regulatory protein glucose concentration glucose homeostasis glucose levels glucose metabolism glucose phosphorylation glucose sensor glucosensing GLUT2 glycogen synthesis glycolysis hepatic hepatic GK hepatic glucokinase hepatic glucose hepatocytes hexokinase homeostasis hormone human hypoglycemia increase induced inhibition insulin granules insulin release insulin secretion interaction isozyme kinase kinetic leucine liver liver glucokinase Magnuson Matschinsky FM mechanism metabolism MODY2 Molecular mouse mRNA Natl Acad Sci neurons normal nuclear overexpression pancreatic cells pancreatic islets pathway patients phosphorylation plasma pregnancy Proc Natl Acad rat hepatocytes receptor residues response role Schaftingen sequence Shiota signaling SREBP-1c stimulation structure studies substrate threshold for GSIR transgenic transgenic mice translocation type 2 diabetes