Glucagon secretion is inhibited by the incretin hormone GLP-1 but the mechanisms remain obscure. Evidence has been presented for paracrine regulation (e.g. via somatostatin released from neighbouring d-cells). This scenario would be consistent with the low expression of GLP-1 receptors in a-cells. In my talk I will present recent data suggesting that GLP-1 exerts a direct effect on glucagon secretion and that the inhibition can occur without any stimulation of insulin or somatostatin release. I will also demonstrate that the inhibitory effect GLP-1 is mimicked by the adenylate cyclase activator forskolin at concentrations as low as 1 nM. I will consider the signal transduction mechanisms involved and present a unifying hypothesis for the regulation of glucagon secretion by glucose and GLP-1.