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Following stimulation, pancreatic beta-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, beta-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 beta-cell function is complicated because of the highly dynamic nature of their intracellular and intercellular signalling as well as insulin release itself. beta-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 beta-cell signalling. An increased understanding of beta-cell signalling might identify new mechanisms underlying insulin release, with relevance for future drug therapy and de novo stem cell engineering of functional islets.

Original publication

DOI

10.1038/s41574-018-0105-2

Type

Journal article

Journal

Nat Rev Endocrinol

Publication Date

2018

Volume

14

Pages

721 - 737

Keywords

Animals Diabetes Mellitus, Type 2/*genetics/*metabolism Genetic Predisposition to Disease/*epidemiology Glucose/metabolism Homeostasis/genetics Humans Incidence Insulin Secretion/*physiology Insulin-Secreting Cells/*metabolism Risk Assessment Sensitivity and Specificity Signal Transduction