Following stimulation, pancreatic β-cells must orchestrate a plethora of signalling events to ensure the appropriate release of insulin and maintenance of normal glucose homeostasis. Failure at any point in this cascade leads to impaired insulin secretion, elevated blood levels of glucose and eventually type 2 diabetes mellitus. Likewise, β-cell replacement or regeneration strategies for the treatment of both type 1 and type 2 diabetes mellitus might fail if the correct cell signalling phenotype cannot be faithfully recreated. However, current understanding of β-cell function is complicated because of the highly dynamic nature of their intracellular and intercellular signalling as well as insulin release itself. β-Cells must precisely integrate multiple signals stemming from multiple cues, often with differing intensities, frequencies and cellular and subcellular localizations, before converging these signals onto insulin exocytosis. In this respect, optical approaches with high resolution in space and time are extremely useful for properly deciphering the complexity of β-cell signalling. An increased understanding of β-cell signalling might identify new mechanisms underlying insulin release, with relevance for future drug therapy and de novo stem cell engineering of functional islets.

Department of Chemical Biology Max Planck Institute for Medical Research Heidelberg Germany

European Molecular Biology Laboratory Cell Biology and Biophysics Unit Heidelberg Germany Department of Physiology and Pharmacology Oregon Health and Science University Portland OR USA

Institute of Metabolism and Systems Research University of Birmingham Birmingham UK Centre for Endocrinology Diabetes and Metabolism Birmingham Health Partners Birmingham UK

Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Prague Czech Republic

Research Laboratory of Electronics Massachusetts Institute of Technology Cambridge MA USA

Research Laboratory of Electronics Massachusetts Institute of Technology Cambridge MA USA Department of Chemistry New York University New York NY USA

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