The islets of Langerhans, discovered by a medical student 121 years ago (1), occupy a pivotal position in the endocrine control of fuel metabolism. In the past decade, research has provided exciting insights into the remarkable sophistication of these microorgans. The purpose of this perspective is to focus upon the complex interactions that take place between islet cells. Communication between adjacent cells of the same type can occur; these interactions have been shown best in pancre-atic B cells. Different celltypes can interact through paracrine mechanisms, in which a secretory product moves a short distance through interstitial fluid to reach a target cell. Communi-cation can also take place via a local vascular portal system within islets and, in addition, there is coordination of function between islets. Delineation of these complicated relationships has contributed to our understanding of normal physiology and the pathogenesis of diabetes mellitus.

Islet anatomy The islets of Langerhans, taken together, can be thought ofas a single organ occupying-1% of the pancreas. The human pancreas contains over 1 million islets, and these typically consist ofabout 2,500 cells, although somemay be collections of only a few cells and othersmay be made up of over 12,000 cells. There is an understandable advantage in having the islet organ placed so that insulin and glucagon are directly secreted into the portal vein, thereby optimizing their control over he-patic function. The potential advantage of having islets diffusely distributed instead of being merged into a singlesolid organ is more mysterious. One suggestion isthat there is a local islet-acinar portal vascularsystem that could allow exocrine tissue to be nourished by islet hormones (2); this may have been important during some stages of evolution. An appreciation of the anatomy of islets is crucial for un-derstanding the function of these complexmicroorgans. Islets have a central core of insulin-containing B cells and a sur-rounding mantle of glucagon-containing A cells, somatostatin containing D cells, and pancreatic polypeptide-containing PP cells (see cover figure). In some mammalian species, such as in horse and even man, the pattern may not be as well defined as in the rat, but the B cells are always clumped together with an