Acyl Ureas as Human Liver Glycogen Phosphorylase Inhibitors for the Treatment of Type 2 Diabetes

2005 ◽  
Vol 48 (20) ◽  
pp. 6178-6193 ◽  
Author(s):  
Thomas Klabunde ◽  
K. Ulrich Wendt ◽  
Dieter Kadereit ◽  
Volker Brachvogel ◽  
Hans-Jörg Burger ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Human Liver ◽  
Glycogen Phosphorylase ◽  
Liver Glycogen ◽  
Glycogen Phosphorylase Inhibitors

Phytogenic Polyphenols as Glycogen Phosphorylase Inhibitors: The Potential of Triterpenes and Flavonoids for Glycaemic Control in Type 2 Diabetes

2017 ◽  
Vol 24 (4) ◽  
pp. 384-403 ◽  
Author(s):  
Demetres Leonidas ◽  
Joseph Hayes ◽  
Atsushi Kato ◽  
Vassiliki Skamnaki ◽  
Demetra Chatzileontiadou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycaemic Control ◽  
Glycogen Phosphorylase ◽  
Glycogen Phosphorylase Inhibitors

scholarly journals Human liver glycogen phosphorylase inhibitors bind at a new allosteric site

2000 ◽  
Vol 7 (9) ◽  
pp. 677-682 ◽  
Author(s):  
Virginia L Rath ◽  
Mark Ammirati ◽  
Dennis E Danley ◽  
Jennifer L Ekstrom ◽  
E Michael Gibbs ◽  
...  
Keyword(s):  
Human Liver ◽  
Glycogen Phosphorylase ◽  
Liver Glycogen ◽  
Allosteric Site ◽  
Glycogen Phosphorylase Inhibitors

Endogenous effectors of human liver glycogen phosphorylase modulate effects of indole-site inhibitors

2005 ◽  
Vol 289 (3) ◽  
pp. E366-E372 ◽  
Author(s):  
Nacide Ercan-Fang ◽  
Miriam R. Taylor ◽  
Judith L. Treadway ◽  
Carolyn B. Levy ◽  
Paul E. Genereux ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Human Liver ◽  
Glycogen Phosphorylase ◽  
Liver Glycogen ◽  
Inhibitory Effect ◽  
Small Molecular Weight ◽  
Glucose Lowering ◽  
Glycogen Phosphorylase Inhibitors

Phosphorylase is regulated by a number of small-molecular-weight effectors that bind to three sites on the enzyme. Recently, a fourth site referred to as the indole-inhibitor site has been identified. Synthetic compounds bind to the site and inhibit activity. However, the effects of these compounds in the presence of other endogenous effectors are unknown. We have determined the effects of four indole derivative glycogen phosphorylase inhibitors (GPI) on recombinant human liver glycogen phosphorylase a activity. The GPIs tested were all potent inhibitors. However, the endogenous inhibitors (glucose, ADP, ATP, fructose 1-phosphate, glucose 6-phosphate, UDP-glucose) and the activator (AMP) markedly reduced the inhibitory effect of GPIs. Consistent with these in vitro findings, the IC50 for the inhibition of glycogenolysis in cells and the liver drug concentration associated with glucose-lowering activity in diabetic ob/ ob mice in vivo were also significantly higher than those determined in in vitro enzyme assays. The inhibitory effect of indole-site effectors is modulated by endogenous small-molecular-weight effectors of phosphorylase a activity. However, at higher concentrations (10–30 μM), the GPI effect was dominant and resulted in inhibition of phosphorylase a activity irrespective of the presence or absence of the other modulators of the enzyme.

Pentacyclic triterpenes, inhibitors of glycogen phosphorylase, as potential drugs for type 2 diabetes: X-ray crystallographic studies

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
SE Zographos ◽  
DD Leonidas ◽  
KM Alexacou ◽  
T Gimisis ◽  
JM Hayes ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycogen Phosphorylase ◽  
X Ray ◽  
Pentacyclic Triterpenes
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