Historical Introduction

In 1869, Paul Langerhans showed that islands of characteristic cells are distributed throughout the pancreas and that these islands are richly innervated.1 After the demonstration that diabetes evolves after pancreatectomy,2 it was suggested in 1901 that the disease is caused by lack of a factor produced by these islets of Langerhans.3 Although several researchers were close to the discovery of insulin, the critical pieces of work in this area were performed by Banting, Best, MacLeod, and Collip in the early 1920s.4 The structure of insulin was established in the 1950s; insulin was the first protein ever to be structurally defined.5 Other landmark discoveries have been the radioimmunoassay determination of insulin in I9606 and the identification of the gene coding for insulin in 1977.7

The islets also produce other regulatory peptides, apart from insulin, and four major hormones are known to be produced by the different islet endocrine cells. The idea that the islets also produce a factor that increases blood glucose was proposed by Murlin and colleagues in 1923,8 although glucagon was not isolated until 1955.9 In 1968, pancreatic polypeptide (PP) was identified,10 and in 1974, it was discovered that the islets also produce somatostatin.11 During the 1980s, the microanatomy of the islets with endocrine cells, nerves, and blood vessels was characterized (Fig. 78-1).12-16 Other contributions to our knowledge of the endocrine pancreas include characterization of the cell biologic processes underlying the exocytosis of the peptide-storing secretory granules (Fig. 78-2),17 the regulation of expression of the islet peptide genes,18 and the understanding of the failure of the B cells as a key contributor to the development of type 2 diabetes.19

The authors have been supported by Swedish Research Council Grant 14X-6834, the Albert Pahlsson, Crafoord, and Novo Nordic Foundations, the Swedish Diabetes Association, and the Faculty of Medicine, Lund University.

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