Protein kinase A-dependent insulinotropic effect of selected flavonoids

International Journal of Biological Macromolecules
Abdul HameedZaheer Ul-Haq

Abstract

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 apigeni...Continue Reading

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