Glucokinase activators (GKAs) promise a new pharmacotherapy for diabetics

F1000 Medicine Reports

Volumn 2, Issue 1, 2010, Pages

  Matschinsky, Franz M ^a   Porte Jr , Daniel ^b,c  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^c VA SAN DIEGO HEALTHCARE SYSTEM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALLOSTERIC GLUCOKINASE ACTIVATOR; ANTIDIABETIC AGENT; GLUCOKINASE; GLUCOSE; UNCLASSIFIED DRUG;

ARTICLE; DRUG MECHANISM; DRUG STRUCTURE; GLUCOSE BLOOD LEVEL; GLUCOSE METABOLISM; HOMEOSTASIS; HUMAN; INSULIN RELEASE; LIVER; MEDICAL RESEARCH; MOLECULAR GENETICS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN;

EID: 77955075939     PISSN: None     EISSN: 17575931     Source Type: Journal    
DOI: 10.3410/M2-43     Document Type: Article

References (22)

1. Matschinsky FM: Assessing the potential of glucokinase activators in diabetes therapy. Nat Rev Drug Discov 2009, 8:399-416.
2. Grimsby J, Sarabu R, Corbett WL, Haynes N-E, Bizzarro FT, Coffey JW, Guertin KR, Hilliard DW, Kester RF, Mahaney PE, Marcus L, Qi L, Spence CL, Tengi J, Magnuson MA, Chu CA, Dvorozniak MT, Matschinsky FM, Grippo JF: Allosteric activators of glucokinase: potential role in diabetes therapy. Science 2003, 301:370-3.
3. Pal M: Recent advances in glucokinase activators for treatment of type 2 diabetes. Drug Discovery Today 2009, 14:784-92.
4. Zhi J, Zhai S, Mulligan ME, Grimsby J, Arbet-Engels C, Boldrin M, Balena R: A novel glucokinase activator RO4389620 improved fasting and postprandial plasma glucose in type 2 diabetic patients. Diabetologia 2008, 51(Suppl 1):S23. Abstract 42.
5. Bonadonna RC, Kapitza C, Heinse T, Avogaro A, Boldrin M, Grimsby J, Mulligan ME, Arbet-Engles C, Balena R: Glucokinase activator RO4389620 improves beta cell function and plasma glucose indexes in patients with type 2 diabetes. Diabetologia 2008, 51(Suppl 1):S371. Abstract 927.
6. Zhai S, Mulligan ME, Grimsby J, Arbet-Engels C, Boldrin M, Balena R, Zhi J: Phase I assessment of a novel glucose activator RO4389620 in healthy male volunteers. Diabetologia 2008, 51 (Suppl 1):S372. Abstract 928.
7. Coghlan M, Leighton B: Glucokinase activators in diabetes management. Expert Opin Investig Drugs 2008, 17:145-67.
8. Guertin KR, Grimsby J: Small molecule glucokinase activators as glucose lowering agents: a new paradigm for diabetes therapy. Curr Med Chem 2006, 13:1839-43.
9. Sarabu R, Berthel SJ, Kester RF, Tilley JW: Glucokinase activators as new type 2 diabetes therapeutic agents. Expert Opin Ther Pat 2008, 18:759-68.
10. Sarabu R, Grimsby J: Targeting glucokinase activation for the treatment of type 2 diabetes - a status review. Curr Opin Drug Discov Devel 2005, 8:631-7. (Pubitemid 41224126)
11. Matschinsky FM, Magnuson MA, Zelent D, Jetton TL, Doliba N, Han Y, Taub R, Grimsby J: The network of glucokinase-expressing cells in glucose homeostasis and the potential of glucokinase activators for diabetes therapy. Diabetes 2006, 55:1-12.
12. Matschinsky FM: Banting Lecture 1995. A lesson in metabolic regulation inspired by the glucokinase glucose sensor paradigm. Diabetes 1996, 45:223-41.
13. Kamata K, Mitsuya M, Nishimura T, Eiki J, Nagata Y: Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase. Structure 2004, 12:429-38. (Pubitemid 38353064)
14. Veiga-da-Cunha M, Van Schaftingen E: Identification of fructose 6-phosphate- and fructose 1-phosphate-binding residues in the regulatory protein of glucokinase. J Biol Chem 2002, 277:8466-73.
15. Agius L: Glucokinase and molecular aspects of liver glycogen metabolism. Biochem J 2008, 414:1-18.
16. Del Guerra S, Lupi R, Marselli L, Masini M, Bugliani M, Sbrana S, Torri S, Polera M, Boggi U: Functional and molecular defects of pancreatic islets in type 2 diabetes. Diabetes 2005, 54:727-35.
17. Danial NN, Gramm CF, Scorrano L, Zhang C-Y, Krauss S, Ranger AM, Datta SR, Greenberg ME, Licklider LJ, Lowell BB, Gygi SP, Korsmeyer SJ: BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 2003, 424:952-6.
18. Danial NN, Walensky LD, Zhang C-Y, Choi CS, Fisher JK, Molina AJA, Datta SR, Pitter KL, Bird GH, Wikstrom JD, Deeney JT, Robertson K, Morash J, Kulkarni A, Neschen S, Kim S, Greenberg ME, Corkey BE, Shirihai OS, Shulman GI, Lowell BB, Korsmeyer SJ: Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nature Med 2008, 14:144-53.
19. Baltrusch S, Wu C, Okar DA, Tiedge M, Lange AJ: Interaction of GK with the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6PF2K/F26P2ase). In Glucokinase and Glycemic Disease: From Basics to Novel Therapeutics. Front Diabetes Vol. 16. Edited by Matschinsky FM, Magnuson MA. Basel: Karger; 2004: 262-74.
20. Brocklehurst KJ, Payne VA, Davies RA, Carroll D, Vertigan HL, Wightman HJ, Aiston S, Waddell ID, Leighton B, Coghlan MP, Agius L: Stimulation of hepatocyte glucose metabolism by novel small molecule glucokinase activators. Diabetes 2004, 53:535-41. (Pubitemid 38270620)
21. Grimsby J, Matschinsky FM, Grippo JF: Discovery and actions of glucokinase activators. In Glucokinase and Glycemic Disease: From Basics to Novel Therapeutics. Front Diabetes. Vol. 16. Edited by Matschinsky FM, Magnuson MA. Basel: Karger; 2004:360-78.
22. Array BioPhama: Glucokinase Activator ARRY-403: Phase 1 Single Ascending Dose Top-Line Results. August 10, 2009. [http://www.arraybiopharma.com/ Documents/PDF/Slides.pdf]