Glucagon is the most important blood glucose-elevating hormone and insulin the only hormone with opposite effect. Whereas scientists agree about the major events of signal transduction in glucose-stimulated insulin secretion, there are fundamentally different ideas how glucose inhibits the release of glucagon. Studies in our laboratory have indicated that both adrenaline stimulation and glucose inhibition of glucagon secretion involve modulation of a Ca²⁺ store-operated mechanism in pancreatic a-cells (Liu et al. 2004, Vieira et al. 2007). We also discovered that excessive glucose concentrations paradoxically stimulate glucagon release in a Ca²⁺-independent manner (Salehi et al. 2006). Evidence is now presented that glucose triggers oscillations of cAMP in mouse a-cells. We have also studied the kinetics of insulin, glucagon and somatostatin secretion from batches of perifused human pancreatic islets. Elevation of glucose from 3 to 20 mM resulted in pulsatile release of all hormones with a periodicity of 7–8 min. A unique feature of the glucagon pulses at 20 mM glucose was that the peaks represented marked stimulation of the release and the nadirs between the peaks pronounced inhibition, resulting in 16 % reduction of time-average secretion. Accordingly, glucose modulation of glucagon secretion seems to reflect alternation between a concentration-dependent inhibition by lowering of Ca²⁺ and stimulation, perhaps involving rise of cAMP. References: Liu, Y.-J., Vieira, E. & Gylfe, E. 2004. Cell Calcium 35, 357–365; Salehi, A., Vieira, E. & Gylfe, E. 2006. Diabetes 55, 2318–2323; Vieira, E., Salehi, A. & Gylfe, E. 2007. Diabetologia 50, 370–379.