Protein kinase A-dependent insulinotropic effect of selected flavonoids.
In the present study, we have estimated the binding affinities of nine flavonoids with cAMP sensing protein kinase A (PKA) by molecular docking. Furthermore, their potential roles in stimulating insulin secretion in a PKA-dependent manner were evaluated in isolated islets using H-89, a PKA inhibitor. Among selected flavonoids, i.e. eriodictyol, kaempferol, hesperetin, naringin, apigenin, hesperidin, quercetin, naringenin and rutin, we found that eriodictyol, kaempferol, and naringenin speculated the best binding interactions with crucial residues in PKA binding pocket. Glucose-dependent insulin secretion was inhibited by eriodictyol, kaempferol and naringenin of 92%, 87%, and 89%, respectively in isolated islets co-incubated with H-89. In contrast, quercetin also got binding with PKA; however, showed no significant PKA-dependent insulinotropic activity in vitro. Rutin showed the least docking interactions with PKA, reflects well in vitro by exhibiting a PKA-independent mode of action. Naringin, hesperetin, hesperidin, and apigenin showed favourable docking affinities with PKA but not with the hot spot residues. Although naringin and hesperetin mimic well in vitro by showing PKA-independent mode of action, hesperidin and apigenin were still exhibited the PKA-dependent effect. The present work suggests that few of the selected flavonoids have strong potential to be used as alternative insulin secretagogues in diabetic treatment.
['Hameed|Abdul|A|', 'Ashraf|Sajda|S|', 'Israr Khan|M|M|', 'Hafizur|Rahman M|RM|', 'Ul-Haq|Zaheer|Z|']
D000818:Animals D001665:Binding Sites D020134:Catalytic Domain D017868:Cyclic AMP-Dependent Protein Kinases D005419:Flavonoids D007328:Insulin D007515:Islets of Langerhans D051379:Mice D062105:Molecular Docking Simulation D056004:Molecular Dynamics Simulation D015394:Molecular Structure D011485:Protein Binding
Flavonoid Protein kinase A Molecular docking Insulin secretion Mice islet