Lannea coromandelica attenuates glucagon and oxyntomodulin mediated cAMP formation in HEK cells stably-expressing human glucagon receptor

Antagonism of glucagon is a potential therapeutic approach for Type 2 diabetes mellitus (T2DM). The bark extract of Lannea coromandelica has been reported to have hypoglycemic or anti-diabetic effects on animal models and human subjects. The aim of this study was to elucidate the molecular mechanisms of L. coromandelica extract as a glucagon receptor antagonist. The aqueous extract of L. coromandelica bark attenuated glucagon-mediated cAMP formation in a concentration dependent manner with an IC50 value of 4.24 ± 1.31 μg/ml. It shifted a concentration response curve of glucagon towards the right with a 4, 21 and 40-fold change in IC50 at 6.25, 12.5 and 25 μg/ml of extract, respectively. Additionally, it attenuated an oxyntomodulin-mediated cAMP response. The extract was found specifically to inhibit glucagon mediated cAMP formation since it was ineffective in reducing cAMP levels nonspecifically-elevated by forskolin. The data support that the aqueous extract of L. coromandelica antagonizes the glucagon receptor and has the potential to reduce glucagon mediated liver glucose output.