title: Alpha-, Delta- and PP-cells: Are They the Architectural Cornerstones of Islet Structure and Co-ordination?
abstract: Islet non-β-cells, the α- δ- and pancreatic polypeptide cells (PP-cells), are important components of islet architecture and intercellular communication. In α-cells, glucagon is found in electron-dense granules; granule exocytosis is calcium-dependent via P/Q-type Ca(2+)-channels, which may be clustered at designated cell membrane sites. Somatostatin-containing δ-cells are neuron-like, creating a network for intra-islet communication. Somatostatin 1-28 and 1-14 have a short bioactive half-life, suggesting inhibitory action via paracrine signaling. PP-cells are the most infrequent islet cell type. The embryologically separate ventral pancreas anlage contains PP-rich islets that are morphologically diffuse and α-cell deficient. Tissue samples taken from the head region are unlikely to be representative of the whole pancreas. PP has anorexic effects on gastro-intestinal function and alters insulin and glucagon secretion. Islet architecture is disrupted in rodent diabetic models, diabetic primates and human Type 1 and Type 2 diabetes, with an increased α-cell population and relocation of non-β-cells to central areas of the islet. In diabetes, the transdifferentiation of non-β-cells, with changes in hormone content, suggests plasticity of islet cells but cellular function may be compromised. Understanding how diabetes-related disordered islet structure influences intra-islet cellular communication could clarify how non-β-cells contribute to the control of islet function.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, United Kingdom. (MFB)
authors.forename: Melissa F
authors.initials: MF
authors.lastname: Brereton
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, United Kingdom. (EV, QZ, AC)
authors.forename: Elisa
authors.initials: E
authors.lastname: Vergari
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, United Kingdom. (EV, QZ, AC)
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, United Kingdom. (EV, QZ, AC)
authors.forename: Anne
authors.initials: A
authors.lastname: Clark
mesh_terms: D000818:Animals; D006801:Humans; D007515:Islets of Langerhans / Q000033:anatomy & histology* / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron
keywords: PP; communication; exocytosis; glucagon; granule; insulin; intra-islet signaling; non-β-cell; paracrine; somatostatin