Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 301 (5631): 370-373

Copyright © 2003 by the American Association for the Advancement of Science

Allosteric Activators of Glucokinase: Potential Role in Diabetes Therapy

Joseph Grimsby,1 Ramakanth Sarabu,1 Wendy L. Corbett,1 Nancy-Ellen Haynes,1 Fred T. Bizzarro,1 John W. Coffey,1 Kevin R. Guertin,1 Darryl W. Hilliard,1* Robert F. Kester,1 Paige E. Mahaney,1{dagger} Linda Marcus,1 Lida Qi,1 Cheryl L. Spence,1 John Tengi,1 Mark A. Magnuson,2 Chang An Chu,1 Mark T. Dvorozniak,1 Franz M. Matschinsky,3 Joseph F. Grippo1{ddagger}

Abstract: 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 ß 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.

1 Department of Metabolic Diseases, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA. 2 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA. 3 Department of Biochemistry and Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Back to Top

* Present address: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.

{dagger} Present address: Chemical Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA.

{ddagger} To whom correspondence should be addressed. E-mail: joseph.grippo{at}roche.com


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Discovery of Small-Molecule Glucokinase Regulatory Protein Modulators That Restore Glucokinase Activity.
K. Chen, K. Michelsen, R. J. M. Kurzeja, J. Han, M. Vazir, D. J. St. Jean Jr., C. Hale, and R. C. Wahl (2014)
J Biomol Screen
   Abstract »    Full Text »    PDF »
A tRNA splicing operon: Archease endows RtcB with dual GTP/ATP cofactor specificity and accelerates RNA ligation.
K. K. Desai, C. L. Cheng, C. A. Bingman, G. N. Phillips Jr, and R. T. Raines (2014)
Nucleic Acids Res. 42, 3931-3942
   Abstract »    Full Text »    PDF »
G0-G1 Transition and the Restriction Point in Pancreatic {beta}-Cells In Vivo.
A. Hija, S. Salpeter, A. Klochendler, J. Grimsby, M. Brandeis, B. Glaser, and Y. Dor (2014)
Diabetes 63, 578-584
   Abstract »    Full Text »    PDF »
Glucokinase Activation Ameliorates ER Stress-Induced Apoptosis in Pancreatic {beta}-Cells.
J. Shirakawa, Y. Togashi, E. Sakamoto, M. Kaji, K. Tajima, K. Orime, H. Inoue, N. Kubota, T. Kadowaki, and Y. Terauchi (2013)
Diabetes 62, 3448-3458
   Abstract »    Full Text »    PDF »
Molecular basis for the role of glucokinase regulatory protein as the allosteric switch for glucokinase.
J. M. Choi, M.-H. Seo, H.-H. Kyeong, E. Kim, and H.-S. Kim (2013)
PNAS 110, 10171-10176
   Abstract »    Full Text »    PDF »
Tolbutamide Controls Glucagon Release From Mouse Islets Differently Than Glucose: Involvement of KATP Channels From Both {alpha}-Cells and {delta}-Cells.
R. Cheng-Xue, A. Gomez-Ruiz, N. Antoine, L. A. Noel, H.-Y. Chae, M. A. Ravier, F. Chimienti, F. C. Schuit, and P. Gilon (2013)
Diabetes 62, 1612-1622
   Abstract »    Full Text »    PDF »
Bcl-2 and Bcl-xL Suppress Glucose Signaling in Pancreatic {beta}-Cells.
D. S. Luciani, S. A. White, S. B. Widenmaier, V. V. Saran, F. Taghizadeh, X. Hu, M. F. Allard, and J. D. Johnson (2013)
Diabetes 62, 170-182
   Abstract »    Full Text »    PDF »
Pancreatic Beta Cells in Very Old Mice Retain Capacity for Compensatory Proliferation.
M. Stolovich-Rain, A. Hija, J. Grimsby, B. Glaser, and Y. Dor (2012)
J. Biol. Chem. 287, 27407-27414
   Abstract »    Full Text »    PDF »
Insights Into the Pathogenicity of Rare Missense GCK Variants From the Identification and Functional Characterization of Compound Heterozygous and Double Mutations Inherited in Cis.
N. L. Beer, K. K. Osbak, M. van de Bunt, N. D. Tribble, A. M. Steele, K. J. Wensley, E. L. Edghill, K. Colcough, A. Barrett, L. Valentinova, et al. (2012)
Diabetes Care 35, 1482-1484
   Abstract »    Full Text »    PDF »
Insights into Mechanism of Glucokinase Activation: OBSERVATION OF MULTIPLE DISTINCT PROTEIN CONFORMATIONS.
S. Liu, M. J. Ammirati, X. Song, J. D. Knafels, J. Zhang, S. E. Greasley, J. A. Pfefferkorn, and X. Qiu (2012)
J. Biol. Chem. 287, 13598-13610
   Abstract »    Full Text »    PDF »
Novel Pharmacological Approaches to the Treatment of Type 2 Diabetes.
E. J. Verspohl (2012)
Pharmacol. Rev. 64, 188-237
   Abstract »    Full Text »    PDF »
Brain Glucose Sensors Play a Significant Role in the Regulation of Pancreatic Glucose-Stimulated Insulin Secretion.
M. A. Osundiji, D. D. Lam, J. Shaw, C.-Y. Yueh, S. P. Markkula, P. Hurst, C. Colliva, A. Roda, L. K. Heisler, and M. L. Evans (2012)
Diabetes 61, 321-328
   Abstract »    Full Text »    PDF »
Glucokinase activation repairs defective bioenergetics of islets of Langerhans isolated from type 2 diabetics.
N. M. Doliba, W. Qin, H. Najafi, C. Liu, C. W. Buettger, J. Sotiris, H. W. Collins, C. Li, C. A. Stanley, D. F. Wilson, et al. (2012)
Am J Physiol Endocrinol Metab 302, E87-E102
   Abstract »    Full Text »    PDF »
Pharmacokinetic and Pharmacodynamic Properties of the Glucokinase Activator MK-0941 in Rodent Models of Type 2 Diabetes and Healthy Dogs.
J.-i. Eiki, Y. Nagata, M. Futamura, K. Sasaki-Yamamoto, T. Iino, T. Nishimura, M. Chiba, S. Ohyama, R. Yoshida-Yoshimioto, K. Fujii, et al. (2011)
Mol. Pharmacol. 80, 1156-1165
   Abstract »    Full Text »    PDF »
Effects of MK-0941, a Novel Glucokinase Activator, on Glycemic Control in Insulin-Treated Patients With Type 2 Diabetes.
G. E. Meininger, R. Scott, M. Alba, Y. Shentu, E. Luo, H. Amin, M. J. Davies, K. D. Kaufman, and B. J. Goldstein (2011)
Diabetes Care 34, 2560-2566
   Abstract »    Full Text »    PDF »
Susceptibility of Glucokinase-MODY Mutants to Inactivation by Oxidative Stress in Pancreatic {beta}-Cells.
K. S. Cullen, F. M. Matschinsky, L. Agius, and C. Arden (2011)
Diabetes 60, 3175-3185
   Abstract »    Full Text »    PDF »
Generation of N-Ethyl-N-nitrosourea (ENU) Diabetes Models in Mice Demonstrates Genotype-specific Action of Glucokinase Activators.
D. Fenner, S. Odili, H.-K. Hong, Y. Kobayashi, A. Kohsaka, S. M. Siepka, M. H. Vitaterna, P. Chen, B. Zelent, J. Grimsby, et al. (2011)
J. Biol. Chem. 286, 39560-39572
   Abstract »    Full Text »    PDF »
Upregulation of {beta}-cell genes and improved function in rodent islets following chronic glucokinase activation.
D. Gill, K. J. Brocklehurst, H. W. G. Brown, and D. M. Smith (2011)
J. Mol. Endocrinol. 47, 59-67
   Abstract »    Full Text »    PDF »
Discovery of a Novel Site Regulating Glucokinase Activity following Characterization of a New Mutation Causing Hyperinsulinemic Hypoglycemia in Humans.
N. L. Beer, M. van de Bunt, K. Colclough, C. Lukacs, P. Arundel, C. L. Chik, J. Grimsby, S. Ellard, and A. L. Gloyn (2011)
J. Biol. Chem. 286, 19118-19126
   Abstract »    Full Text »    PDF »
Glucokinase Activators for Diabetes Therapy: May 2010 status report.
F. M. Matschinsky, B. Zelent, N. Doliba, C. Li, J. M. Vanderkooi, A. Naji, R. Sarabu, and J. Grimsby (2011)
Diabetes Care 34, S236-S243
   Full Text »    PDF »
Cardiac Myosin Activation: A Potential Therapeutic Approach for Systolic Heart Failure.
F. I. Malik, J. J. Hartman, K. A. Elias, B. P. Morgan, H. Rodriguez, K. Brejc, R. L. Anderson, S. H. Sueoka, K. H. Lee, J. T. Finer, et al. (2011)
Science 331, 1439-1443
   Abstract »    Full Text »    PDF »
Glucose and aging control the quiescence period that follows pancreatic beta cell replication.
S. J. Salpeter, A. M. Klein, D. Huangfu, J. Grimsby, and Y. Dor (2010)
Development 137, 3205-3213
   Abstract »    Full Text »    PDF »
Clinical Heterogeneity in Monogenic Diabetes Caused by Mutations in the Glucokinase Gene (GCK-MODY).
A. L. Cuesta-Munoz, T. Tuomi, N. Cobo-Vuilleumier, H. Koskela, S. Odili, A. Stride, C. Buettger, T. Otonkoski, P. Froguel, J. Grimsby, et al. (2010)
Diabetes Care 33, 290-292
   Abstract »    Full Text »    PDF »
The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver.
N. L. Beer, N. D. Tribble, L. J. McCulloch, C. Roos, P. R. V. Johnson, M. Orho-Melander, and A. L. Gloyn (2009)
Hum. Mol. Genet. 18, 4081-4088
   Abstract »    Full Text »    PDF »
Extremes of Clinical and Enzymatic Phenotypes in Children With Hyperinsulinism Caused by Glucokinase Activating Mutations.
S. Sayed, D. R. Langdon, S. Odili, P. Chen, C. Buettger, A. B. Schiffman, M. Suchi, R. Taub, J. Grimsby, F. M. Matschinsky, et al. (2009)
Diabetes 58, 1419-1427
   Abstract »    Full Text »    PDF »
Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo.
Y. Fujita, R. D. Wideman, M. Speck, A. Asadi, D. S. King, T. D. Webber, M. Haneda, and T. J. Kieffer (2009)
Am J Physiol Endocrinol Metab 296, E473-E479
   Abstract »    Full Text »    PDF »
BLX-1002, a novel thiazolidinedione with no PPAR affinity, stimulates AMP-activated protein kinase activity, raises cytosolic Ca2+, and enhances glucose-stimulated insulin secretion in a PI3K-dependent manner.
F. Zhang, D. Dey, R. Branstrom, L. Forsberg, M. Lu, Q. Zhang, and A. Sjoholm (2009)
Am J Physiol Cell Physiol 296, C346-C354
   Abstract »    Full Text »    PDF »
Biophysical Characterization of the Interaction between Hepatic Glucokinase and Its Regulatory Protein: IMPACT OF PHYSIOLOGICAL AND PHARMACOLOGICAL EFFECTORS.
O. Anderka, J. Boyken, U. Aschenbach, A. Batzer, O. Boscheinen, and D. Schmoll (2008)
J. Biol. Chem. 283, 31333-31340
   Abstract »    Full Text »    PDF »
Activation and Translocation of Glucokinase in Rat Primary Hepatocytes Monitored by High Content Image Analysis.
M. Wolff, S. G. Kauschke, S. Schmidt, and R. Heilker (2008)
J Biomol Screen 13, 837-846
   Abstract »    PDF »
Activating glucokinase (GCK) mutations as a cause of medically responsive congenital hyperinsulinism: prevalence in children and characterisation of a novel GCK mutation..
H. B T Christesen, N. D Tribble, A. Molven, J. Siddiqui, T. Sandal, K. Brusgaard, S. Ellard, P. R Njolstad, J. Alm, B. Brock Jacobsen, et al. (2008)
Eur. J. Endocrinol. 159, 27-34
   Abstract »    Full Text »    PDF »
Liver-specific Knockdown of JNK1 Up-regulates Proliferator-activated Receptor {gamma} Coactivator 1beta and Increases Plasma Triglyceride despite Reduced Glucose and Insulin Levels in Diet-induced Obese Mice.
R. Yang, D. M. Wilcox, D. L. Haasch, P. M. Jung, P. T. Nguyen, M. J. Voorbach, S. Doktor, S. Brodjian, E. N. Bush, E. Lin, et al. (2007)
J. Biol. Chem. 282, 22765-22774
   Abstract »    Full Text »    PDF »
Allosteric Activation of Human Glucokinase by Free Polyubiquitin Chains and Its Ubiquitin-dependent Cotranslational Proteasomal Degradation.
L. Bjorkhaug, J. Molnes, O. Sovik, P. R. Njolstad, and T. Flatmark (2007)
J. Biol. Chem. 282, 22757-22764
   Abstract »    Full Text »    PDF »
Cell Biology Assessment of Glucokinase Mutations V62M and G72R in Pancreatic {beta}-Cells: Evidence for Cellular Instability of Catalytic Activity.
C. Arden, A. Trainer, N. de la Iglesia, K. T. Scougall, A. L. Gloyn, A. J. Lange, J. A.M. Shaw, F. M. Matschinsky, and L. Agius (2007)
Diabetes 56, 1773-1782
   Abstract »    Full Text »    PDF »
Immunohistochemical Evidence for the Presence of Glucokinase in the Gonadotropes and Thyrotropes of the Anterior Pituitary Gland of Rat and Monkey.
R. L. Sorenson, L. E. Stout, T. C. Brelje, T. L. Jetton, and F. M. Matschinsky (2007)
Journal of Histochemistry & Cytochemistry 55, 555-566
   Abstract »    Full Text »    PDF »
Glucose-Dependent Modulation of Insulin Secretion and Intracellular Calcium Ions by GKA50, a Glucokinase Activator.
D. Johnson, R. M. Shepherd, D. Gill, T. Gorman, D. M. Smith, and M. J. Dunne (2007)
Diabetes 56, 1694-1702
   Abstract »    Full Text »    PDF »
Bisphosphonates as Inhibitors of Trypanosoma cruzi Hexokinase: KINETIC AND METABOLIC STUDIES.
C. E. Sanz-Rodriguez, J. L. Concepcion, S. Pekerar, E. Oldfield, and J. A. Urbina (2007)
J. Biol. Chem. 282, 12377-12387
   Abstract »    Full Text »    PDF »
For the ZDF rat, "Breaking Up Is Hard To Do": dissociation of the GK:GKRP complex.
A. J. Lange (2007)
Am J Physiol Regulatory Integrative Comp Physiol 292, R1379-R1380
   Full Text »    PDF »
Biochemical Basis of Glucokinase Activation and the Regulation by Glucokinase Regulatory Protein in Naturally Occurring Mutations.
V. V. Heredia, T. J. Carlson, E. Garcia, and S. Sun (2006)
J. Biol. Chem. 281, 40201-40207
   Abstract »    Full Text »    PDF »
An Allosteric Activator of Glucokinase Impairs the Interaction of Glucokinase and Glucokinase Regulatory Protein and Regulates Glucose Metabolism.
M. Futamura, H. Hosaka, A. Kadotani, H. Shimazaki, K. Sasaki, S. Ohyama, T. Nishimura, J.-i. Eiki, and Y. Nagata (2006)
J. Biol. Chem. 281, 37668-37674
   Abstract »    Full Text »    PDF »
Glucokinase Regulatory Network in Pancreatic {beta}-Cells and Liver.
S. Baltrusch and M. Tiedge (2006)
Diabetes 55, S55-S64
   Abstract »    Full Text »    PDF »
Epigallocatechin Gallate Supplementation Alleviates Diabetes in Rodents.
S. Wolfram, D. Raederstorff, M. Preller, Y. Wang, S. R. Teixeira, C. Riegger, and P. Weber (2006)
J. Nutr. 136, 2512-2518
   Abstract »    Full Text »    PDF »
Conformational transition pathway in the allosteric process of human glucokinase.
J. Zhang, C. Li, K. Chen, W. Zhu, X. Shen, and H. Jiang (2006)
PNAS 103, 13368-13373
   Abstract »    Full Text »    PDF »
Whence cometh the allosterome?.
J. E. Lindsley and J. Rutter (2006)
PNAS 103, 10533-10535
   Abstract »    Full Text »    PDF »
A glucose sensor role for glucokinase in anterior pituitary cells..
D. Zelent, M. L. Golson, B. Koeberlein, R. Quintens, L. van Lommel, C. Buettger, H. Weik-Collins, R. Taub, J. Grimsby, F. Schuit, et al. (2006)
Diabetes 55, 1923-1929
   Abstract »    Full Text »    PDF »
From Clinicogenetic Studies of Maturity-Onset Diabetes of the Young to Unraveling Complex Mechanisms of Glucokinase Regulation.
J. V. Sagen, S. Odili, L. Bjorkhaug, D. Zelent, C. Buettger, J. Kwagh, C. Stanley, K. Dahl-Jorgensen, C. de Beaufort, G. I. Bell, et al. (2006)
Diabetes 55, 1713-1722
   Abstract »    Full Text »    PDF »
Inhibition of Fructose 1,6-Bisphosphatase Reduces Excessive Endogenous Glucose Production and Attenuates Hyperglycemia in Zucker Diabetic Fatty Rats.
P. D. van Poelje, S. C. Potter, V. C. Chandramouli, B. R. Landau, Q. Dang, and M. D. Erion (2006)
Diabetes 55, 1747-1754
   Abstract »    Full Text »    PDF »
5-Aminoimidazole-4-Carboxamide-1-{beta}-D-Ribofuranoside and Metformin Inhibit Hepatic Glucose Phosphorylation by an AMP-Activated Protein Kinase-Independent Effect on Glucokinase Translocation..
B. Guigas, L. Bertrand, N. Taleux, M. Foretz, N. Wiernsperger, D. Vertommen, F. Andreelli, B. Viollet, and L. Hue (2006)
Diabetes 55, 865-874
   Abstract »    Full Text »    PDF »
Glucokinase Is a Critical Regulator of Ventromedial Hypothalamic Neuronal Glucosensing.
L. Kang, A. A. Dunn-Meynell, V. H. Routh, L. D. Gaspers, Y. Nagata, T. Nishimura, J. Eiki, B. B. Zhang, and B. E. Levin (2006)
Diabetes 55, 412-420
   Abstract »    Full Text »    PDF »
The Network of Glucokinase-Expressing Cells in Glucose Homeostasis and the Potential of Glucokinase Activators for Diabetes Therapy.
F. M. Matschinsky, M. A. Magnuson, D. Zelent, T. L. Jetton, N. Doliba, Y. Han, R. Taub, and J. Grimsby (2006)
Diabetes 55, 1-12
   Abstract »    Full Text »    PDF »
Leucine Regulation of Glucokinase and ATP Synthase Sensitizes Glucose-Induced Insulin Secretion in Pancreatic {beta}-Cells.
J. Yang, R. K. Wong, M. Park, J. Wu, J. R. Cook, D. A. York, S. Deng, J. Markmann, A. Naji, B. A. Wolf, et al. (2006)
Diabetes 55, 193-201
   Abstract »    Full Text »    PDF »
Intragenic Suppression of Gal3C Interaction With Gal80 in the Saccharomyces cerevisiae GAL Gene Switch.
C. Q. Diep, G. Peng, M. Bewley, V. Pilauri, I. Ropson, and J. E. Hopper (2006)
Genetics 172, 77-87
   Abstract »    Full Text »    PDF »
Interaction of Glucokinase With the Liver Regulatory Protein Is Conferred by Leucine-Asparagine Motifs of the Enzyme.
S. Baltrusch, F. Francini, S. Lenzen, and M. Tiedge (2005)
Diabetes 54, 2829-2837
   Abstract »    Full Text »    PDF »
Insights into the Structure and Regulation of Glucokinase from a Novel Mutation (V62M), Which Causes Maturity-onset Diabetes of the Young.
A. L. Gloyn, S. Odili, D. Zelent, C. Buettger, H. A. J. Castleden, A. M. Steele, A. Stride, C. Shiota, M. A. Magnuson, R. Lorini, et al. (2005)
J. Biol. Chem. 280, 14105-14113
   Abstract »    Full Text »    PDF »
Increased Potency and Efficacy of Combined Phosphorylase Inactivation and Glucokinase Activation in Control of Hepatocyte Glycogen Metabolism.
L. J. Hampson and L. Agius (2005)
Diabetes 54, 617-623
   Abstract »    Full Text »    PDF »
Leucine Culture Reveals That ATP Synthase Functions as a Fuel Sensor in Pancreatic {beta}-Cells.
J. Yang, R. K. Wong, X. Wang, J. Moibi, M. J. Hessner, S. Greene, J. Wu, S. Sukumvanich, B. A. Wolf, and Z. Gao (2004)
J. Biol. Chem. 279, 53915-53923
   Abstract »    Full Text »    PDF »
Pathways in Beta-Cell Stimulus-Secretion Coupling as Targets for Therapeutic Insulin Secretagogues.
J.-C. Henquin (2004)
Diabetes 53, S48-S58
   Abstract »    Full Text »    PDF »
Discovery of an allosteric site in the caspases.
J. A. Hardy, J. Lam, J. T. Nguyen, T. O'Brien, and J. A. Wells (2004)
PNAS 101, 12461-12466
   Abstract »    Full Text »    PDF »
Does the Glucose-Dependent Insulin Secretion Mechanism Itself Cause Oxidative Stress in Pancreatic {beta}-Cells?.
L. E. Fridlyand and L. H. Philipson (2004)
Diabetes 53, 1942-1948
   Abstract »    Full Text »    PDF »
Severe Persistent Hyperinsulinemic Hypoglycemia due to a De Novo Glucokinase Mutation.
A. L. Cuesta-Munoz, H. Huopio, T. Otonkoski, J. M. Gomez-Zumaquero, K. Nanto-Salonen, J. Rahier, S. Lopez-Enriquez, M. A. Garcia-Gimeno, P. Sanz, F. C. Soriguer, et al. (2004)
Diabetes 53, 2164-2168
   Abstract »    Full Text »    PDF »
G(-30)A Polymorphism in the Pancreatic Promoter of the Glucokinase Gene Associated With Angiographic Coronary Artery Disease and Type 2 Diabetes Mellitus.
W. Marz, M. Nauck, M. M. Hoffmann, D. Nagel, B. O. Boehm, W. Koenig, D. Rothenbacher, and B. R. Winkelmann (2004)
Circulation 109, 2844-2849
   Abstract »    Full Text »    PDF »
Hepatic Glucokinase Is Required for the Synergistic Action of ChREBP and SREBP-1c on Glycolytic and Lipogenic Gene Expression.
R. Dentin, J.-P. Pegorier, F. Benhamed, F. Foufelle, P. Ferre, V. Fauveau, M. A. Magnuson, J. Girard, and C. Postic (2004)
J. Biol. Chem. 279, 20314-20326
   Abstract »    Full Text »    PDF »
Interaction of 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase (PFK-2/FBPase-2) With Glucokinase Activates Glucose Phosphorylation and Glucose Metabolism in Insulin-Producing Cells.
L. Massa, S. Baltrusch, D. A. Okar, A. J. Lange, S. Lenzen, and M. Tiedge (2004)
Diabetes 53, 1020-1029
   Abstract »    Full Text »    PDF »
Stimulation of Hepatocyte Glucose Metabolism by Novel Small Molecule Glucokinase Activators.
K. J. Brocklehurst, V. A. Payne, R. A. Davies, D. Carroll, H. L. Vertigan, H. J. Wightman, S. Aiston, I. D. Waddell, B. Leighton, M. P. Coghlan, et al. (2004)
Diabetes 53, 535-541
   Abstract »    Full Text »    PDF »
Permanent Neonatal Diabetes Caused by Glucokinase Deficiency: Inborn Error of the Glucose-Insulin Signaling Pathway.
P. R. Njolstad, J. V. Sagen, L. Bjorkhaug, S. Odili, N. Shehadeh, D. Bakry, S. U. Sarici, F. Alpay, J. Molnes, A. Molven, et al. (2003)
Diabetes 52, 2854-2860
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882