Biochemical and biological assessment of the inhibitory potency of extracts from vinification byproducts of Vitis vinifera extracts against glycogen phosphorylase

Extracts and flavonoids from onion inhibit the intestinal sodium-coupled glucose transporter 1 (SGLT1) in vitro but show no anti-hyperglycaemic effects in vivo in normoglycaemic mice and human volunteers

“…For quercetin, glucose-induced insulin release from isolated rat pancreatic islets revealed an increase (Bardy et al, 2013;Hii & Howell, 1985;Youl et al, 2010). As an example for effects in target tissues of insulin may be the recent in vitro study that revealed that extracts from vinification byproducts of Vitis vinifera with quercetin as the dominant constituent significantly inhibited glycogen phosphorylase (GP), an enzyme that catalyzes the first step of intracellular degradation of glycogen to glucose-1-phosphate and the hepatic release of glucose (Kantsadi et al, 2014). GP inhibitors have been suggested as new hypoglycaemic agents for treatment of T2DM (Treadway, Mendys, & Hoover, 2001) similar to inhibitors of hepatic glucose-6-phosphatase, an enzyme involved in the glucose release from glucose-6-phosphate as the final step in gluconeogenesis and glycogenolysis (Arion et al, 1997;Herling et al, 1998).…”

Natural flavonoids as antidiabetic agents. The binding of gallic and ellagic acids to glycogen phosphorylase b

“…Chrysin (Table 1), a natural occurring flavonoid, is a potent inhibitor ( K i = 19 μM) that also binds to the inhibitor site [19], while another flavonoid inhibitor, quercetagetin, binds to the allosteric site [20]. A recent screening of thirteen polyphenolic extracts obtained from the vinification byproducts of Vitis vinifera against GP revealed that the most active ingredient of these extracts is quercetin which binds to a novel binding site, distinct from the other known sites of the enzyme [7]. One of the most potent natural flavonoid inhibitors of GP is ellagic acid with an IC 50 value of 3.2 μM [20].…”

Computationally motivated synthesis and enzyme kinetic evaluation of N-(β-d-glucopyranosyl)-1,2,4-triazolecarboxamides as glycogen phosphorylase inhibitors

“…The smaller Ar group (phenyl) of 5a also permits a ipped 1,2,4-triazole conformation (u ¼ À176. 7 ) shown in Fig. 4, where the triazole NH is a little longer than hydrogen bonding distance from the Glu88 sidechain carboxylate (distance $ 3.3Å).…”

“…3 It is an allosteric enzyme with a number of different binding sites, 4,5 the catalytic, allosteric, new allosteric, inhibitor, glycogen storage, benzimiadazole 6 and the very recently identied quercetin binding site. 7 Signicant efforts have been afforded to the design of GP inhibitors in recent years, with catalytic site inhibitors the most explored. 4,8,9 The physiological inhibitor of GP is a-D-glucose (K i ¼ 1.7 mM), but bsubstitutions at the anomeric carbon of D-glucose have led to the most effective GP catalytic site inhibitors and have demonstrated blood sugar lowering effects in vivo.…”