The current dogma says
that the pancreatic hormone glucagon works by activating adenylate cyclase,
and generating cyclic AMP, in target tissues. We recently published a
paper casting serious doubt on that view. Rather than acting as an
“anti-insulin”, glucagon appears to actually imitate or duplicate effects
of insulin on the heart and perhaps on other non-liver tissues as well. We
will be conducting experiments this summer designed to test the hypothesis
that glucagon promotes glucose output from the liver and glucose
utilization in the heart by mechanisms that are totally independent of
cyclic AMP, and that may involve the activation of an unknown receptor.
The results of this project will be of fundamental importance not only for
our understanding of the true mechanism of action of this critical
metabolic hormone, but also for developing new lines of treatment of
diabetes and related metabolic disorders.
