The interplay between cyclic AMP and ions in the stimulus-secretion coupling in pancreatic B-cells

In 1965, Samols et al. reported that administration of glucagon to man increases plasma insulin levels before any change in plasma glucose levels. This observation was the first indirect evidence that cyclic adenosine monophosphate (cAMP) might play a role in the control of insulin secretion. Later on, experiments in vitro using various experimental models demonstrated that exogenous cAMP, stimulators of the adenylate cyclase and inhibitors of the cAMP phosphodiesterase were all able to potentiate glucose-induced insulin release (Grodsky et al., 1967; Lambert et al., 1967; Malaisse et al., 1967; Sussman & Vaughan, 1967; Turtle et al., 1967). At about the same time, the essential rôle of Ca2+ in the stimulation of insulin release was recognized (Grodsky & Bennett, 1966; Milner & Hales, 1967). A few years later, Rasmussen (1970) underlined the multiple relationships between cAMP and Ca2+ and formulated the thesis that both messengers usually act in concert to couple the stimulus recognition to the cell response. This viewpoint was rapidly extended to the pancreatic B-cell (Brisson et al., 1972).