Islets of Langerhans have the characteristic of precisely sensing changes in blood glucose concentration and transferring this signal to adequate secretion of pancreatic hormones. Insulin, which is produced by pancreatic β-cells, is responsible for lowering blood glucose, whereas glucagon, the hormone of pancreatic α-cells, antagonizes most of the effects of insulin. A third hormone, secreted by δ-cells of pancreatic islets, is somatostatin. Besides their endocrine function, insulin, glucagon and somatostatin influence each other by paraand/or autocrine mechanisms. On the level of single cells, the sequences of events leading to exocytosis of insulin or glucagon have been extensively characterized whereas there is less knowledge about mechanisms regulating somatostatin release. Electrical excitability is a key feature of all three cell types (Drews et al. 2010). Glucose stimulation of β-cells induces electrical activity and the intensity of membrane depolarization strictly depends on the concentration of the nutrient stimulus. With respect to glucagon the predominant role of this hormone is to counteract situations of hypoglycaemia. Consequently, rising concentrations of blood glucose and hyperglycaemia are accompanied by suppression of glucagon secretion. This feedback is disturbed in patients suffering from diabetes mellitus type 2. An excess of glucagon together with insufficient insulin secretion and insulin resistance are the basis of the imbalance between glucose-lowering and glucose-elevating mechanisms. Glucose, as well as stimulating β-cells, changes the activity of α-cells. Induction of electrical activity and subsequent Ca2+ influx are features shared by α-and β-cells with regard to initiation of hormone release. But although both cell types are equipped with ATP-dependent K+ channels, which are closed by increased substrate metabolism, the net effect in response to elevated plasma glucose concentration is contrarious. This indicates a completely different function of these channels in α-cells with respect to their regulatory role for glucose dependence of exocytosis (Zhang et al. 2013; Gylfe, 2016). Besides intrinsic factors, paracrine mediators (eg somatostatin, γ-aminobutyric acid, insulin and Zn2+) have been suggested to contribute to the regulation of α-cells. Currently, the impact of these different pathways and whether they act in parallel or are arranged in a hierarchy remain to be elucidated. The best method to investigate paracrine pathways in the complex network of α-, β-and δ-cells is to monitor cellular activity within their natural environment, ie in the intact islet. This is very difficult and requires reliable activation and monitoring of one single cell type in this mini-organ. In a study published in this issue of The Journal of Physiology, Briant and colleagues (2018) use an elegant and sophisticated approach addressing this challenge by optogenetics. This technique takes advantage of light-activated proteins, channelrhodopsins, allowing cells to be ‘switched on and off’not by their physiological regulators but just by light (Nagel et al. 2003). Optogenetic methods have turned out to be a valuable tool for investigation and manipulation of neuronal circuits. This approach is now successfully used to investigate electrical coupling in islets of Langerhans. β-Cell-specific expression of channelrhodopsin-2 enabled exclusive light-induced membrane depolarization of the insulin-producing cells. Concomitant recording of δ-and α-cells localized in the same islet revealed rapid induction of action potentials in δ-cells within a few milliseconds, whereas α-cells were hyperpolarized with a clear delay of 10 s. Based on the fast transfer of the signal, the authors …