Inhibition of hepatic neoglucogenesis and glucose-6-phosphatase by quercetin 3-O-alpha(2''-galloyl)rhamnoside isolated from Bauhinia megalandra leaves.
In intact microsomes, quercetin 3-O-alpha-(2''-galloyl)rhamnoside (QGR) inhibits glucose-6-phosphatase (G-6-Pase) in a concentration-dependent manner. QGR increased the G-6-Pase K(m) for glucose-6-phosphate without change in the V(max). The flavonol did not change the kinetic parameters of disrupted microsomal G-6-Pase or intact or disrupted microsomal G-6-Pase pyrophosphatase (PPase) activity. This result allowed the conclusion that QGR competitively inhibits the glucose-6-phosphate (G-6-P) transporter (T1) without affecting the catalytic subunit or the phosphate/pyrophosphate transporter (T2) of the G-6-Pase system.QGR strongly inhibits the neoglucogenic capacity of rat liver slices incubated in a Krebs-Ringer bicarbonate buffer, supplemented with lactate and oleate saturated albumin. The QGR G-6-Pase inhibition might explain the decrease in the liver slice neoglucogenic capacity and, in turn, could reduce glucose levels in diabetic patients.
Gonzalez-Mujica
Freddy
F
Sección de Bioquímica Médica, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela. gonzalef@latinmail.com
Motta
Norma
N
Estrada
Omar
O
Perdomo
Elsa
E
Méndez
Jeannette
J
Hasegawa
Masahisa
M
D000818:Animals; D017920:Antiporters / Q000187:drug effects; D036481:Bauhinia; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005943:Gluconeogenesis / Q000187:drug effects*; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009004:Monosaccharide Transport Proteins / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D017920:Antiporters; D004791:Enzyme Inhibitors; D009004:Monosaccharide Transport Proteins; D010936:Plant Extracts; C111261:glucose 6-phosphate(transporter); D011794:Quercetin; D005952:Glucose-6-Phosphatase