Glucagon activates two distinct signal transduction systems in hepatocytes, which leads to the desensitization of G-protein-regulated adenylate cyclase, the phosphorylation and inactivation of G_i-2 and the phosphorylation and stimulation of a specific cyclic AMP phosphodiesterase

Summary

A transient increase in the intracellular concentrations of cyclic AMP occurs as a result of the challenge of hepatocytes with glucagon. This event is determined by the initial rapid activation of adenylate cyclase, which is responsible for the production of cyclic AMP within the cell. Following on from this we observe the desensitization of adenylate cyclase; the A-kinase-mediated activation of the ‘dense-vesicle’, high affinity cyclic AMP phosphodiesterase; the phosphorylation and functional inactivation of the inhibitory G-protein G_i-2 and the establishment of a ‘selective’ insulin-resistant state. These events identify ‘interplay’ or ‘cross-talk’ occurring between distinct cellular signalling systems.

These normal physiological controls are identified as being affected in the insulin resistant states that characterize the pathophysiological states conditions of diabetes and obese.