Islet-cell-to-cell communication as basis for normal insulin secretion

The emergence of pancreatic islets has necessitated the development of a signalling system for the intra- and inter-islet coordination of β cells. With evolution, this system has evolved into a complex regulatory network of partially cross-talking pathways, whereby individual cells sense the state of activity of their neighbours and, accordingly, regulate their own level of functioning. A consistent feature of this network in vertebrates is the expression of connexin (Cx)-36-made cell-to-cell channels, which cluster at gap junction domains of the cell membrane, and which adjacent β cells use to share cytoplasmic ions and small metabolites within individual islets. This chapter reviews what is known about Cx36, and the mechanism whereby this β-cell connexin significantly regulates insulin secretion. It further outlines other less established functions of the protein and evaluates its potential relevance for the development of novel therapeutic approaches to diabetes.