title: Targeting glucokinase activation for the treatment of type 2 diabetes--a status review.
abstract: Glucokinase (GK) plays a key role in glucose homeostasis. Developments over the past decade, such as the determination of the function of GK regulatory protein, the discovery of GK mutations related to maturity onset of diabetes of the young, permanent neonatal diabetes mellitus and persistent hyperinsulinemia hypoglycemia of infancy, and the discovery of novel GK activators (GKAs) and their X-ray co-crystal structures with GK, have significantly enhanced our understanding of GK structure and function. This review discusses key publications on GKAs that report full characterization, key compound disclosures from patents, and a current hypothesis on the mechanism of GK activation based on the co-crystal structures of GK-GKA complexes.
authors.affiliation: Hoffmann-La Roche Inc, Department of Discovery Chemistry, Roche Research Center, 340 Kingsland Street, Nutley, NJ 07110, USA. ramakanth.sarabu@roche.com
authors.forename: Ramakanth
authors.initials: R
authors.lastname: Sarabu
authors.forename: Joseph
authors.initials: J
authors.lastname: Grimsby
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005941:Glucokinase / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D007004:Hypoglycemic Agents; D005941:Glucokinase