Sensing Intra‐ and Extra‐Cellular Ca2+ in the Islet of Langerhans

Calcium ions (Ca2+) take part in intra‐ and inter‐cellular signaling to mediate cellular functions. Sensing this ubiquitous messenger is instrumental in disentangling the specific functions of cellular sub‐compartments and/or intercellular communications. In this review, the authors first describe intra‐ and inter‐cellular Ca2+ signaling in relation to insulin secretion from the pancreatic islets, and then outline the development of diverse sensors, for example, chemically synthesized indicators, genetically encoded proteins, and ion‐selective microelectrodes, for intra‐ and extra‐cellular sensing of Ca2+. Particular emphasis is placed on emerging approaches in this field, such as low‐affinity Ca2+ indicators and unique Ca2+‐responsive composite materials. The authors conclude by remarking on the challenges and opportunities for further developments in this field, which may facilitate a more comprehensive understanding of Ca2+ signaling within and outside the islets, and its relevance in health and disease. This review describes the development and current status of Ca2+ sensors in tracing intra‐ and extra‐cellular Ca2+, with a focus on the relevance of Ca2+ signaling to insulin secretion in the islet of Langerhans. Insights into Ca+ sensors have a high potential to facilitate their advancement toward improved understanding of the molecular mechanisms underpinning cellular functions.