Science (American Association for the Advancement of Science), 2003-07, Vol.301 (5631), p.370-373
- Grimsby, Joseph
- Sarabu, Ramakanth
- Corbett, Wendy L.
- Haynes, Nancy-Ellen
- Bizzarro, Fred T.
- Coffey, John W.
- Guertin, Kevin R.
- Hilliard, Darryl W.
- Kester, Robert F.
- Mahaney, Paige E.
- Marcus, Linda
- Qi, Lida
- Spence, Cheryl L.
- Tengi, John
- Magnuson, Mark A.
- Chu, Chang An
- Dvorozniak, Mark T.
- Matschinsky, Franz M.
- Grippo, Joseph F.
2003
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- Autor(en) / Beteiligte
- Grimsby, Joseph
- Sarabu, Ramakanth
- Corbett, Wendy L.
- Haynes, Nancy-Ellen
- Bizzarro, Fred T.
- Coffey, John W.
- Guertin, Kevin R.
- Hilliard, Darryl W.
- Kester, Robert F.
- Mahaney, Paige E.
- Marcus, Linda
- Qi, Lida
- Spence, Cheryl L.
- Tengi, John
- Magnuson, Mark A.
- Chu, Chang An
- Dvorozniak, Mark T.
- Matschinsky, Franz M.
- Grippo, Joseph F.
- Titel
- Allosteric Activators of Glucokinase: Potential Role in Diabetes Therapy
- Ist Teil von
- Science (American Association for the Advancement of Science), 2003-07, Vol.301 (5631), p.370-373
- Ort / Verlag
- Washington, DC: American Association for the Advancement of Science
- Erscheinungsjahr
- 2003
- Quelle
- Science Online_科学在线
- Beschreibungen/Notizen
- Glucokinase (GK) plays a key role in whole-body glucose homeostasis by catalyzing the phosphorylation of glucose in cells that express this enzyme, such as pancreatic β cells and hepatocytes. We describe a class of antidiabetic agents that act as nonessential, mixed-type GK activators (GKAs) that increase the glucose affinity and maximum velocity (Vmax) of GK. GKAs augment both hepatic glucose metabolism and glucose-induced insulin secretion from isolated rodent pancreatic islets, consistent with the expression and function of GK in both cell types. In several rodent models of type 2 diabetes mellitus, GKAs lowered blood glucose levels, improved the results of glucose tolerance tests, and increased hepatic glucose uptake. These findings may lead to the development of new drug therapies for diabetes.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.1084073Titel-ID: cdi_proquest_miscellaneous_743260599
- Format
- –
- Schlagworte
- Adaptor Proteins, Signal Transducing, Allosteric Regulation, Animals, Biological and medical sciences, Blood glucose, Blood Glucose - metabolism, Care and treatment, Carrier Proteins, Circles, Diabetes, Diabetes Mellitus, Type 2 - drug therapy, Diabetes Mellitus, Type 2 - metabolism, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Drug therapy, Enzyme Activation, Enzyme Activators - chemistry, Enzyme Activators - pharmacology, Enzymes, Fundamental and applied biological sciences. Psychology, Glucokinase - metabolism, Glucose, Glucose - metabolism, Glucose Tolerance Test, Hepatocytes, Homeostasis, Humans, Hypoglycemic Agents - chemistry, Hypoglycemic Agents - pharmacology, Insulin, Insulin - blood, Insulin - metabolism, Insulin Secretion, Islets of Langerhans - drug effects, Islets of Langerhans - metabolism, Keto Acids - metabolism, Liver - drug effects, Liver - metabolism, Liver Glycogen - biosynthesis, Male, Metabolism, Mice, Mice, Inbred C57BL, Mice, Obese, Molecular and cellular biology, Patients, Proteins - metabolism, Proteins - pharmacology, Rats, Rats, Wistar, Recombinant Proteins - metabolism, Stereoisomerism, Thiazoles - chemistry, Thiazoles - pharmacology, Type 2 diabetes, Type 2 diabetes mellitus, Vehicles