Characterization of human islet cells: functional and transcriptional studies

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Pancreatic islets play a central role in plasma glucose regulation. They do so by secreting several hormones with key role in glucose homeostasis. In addition, the islet delta-cells secrete somatostatin, a peptide hormone that inhibits both insulin and glucagon release. Type-2 diabetes involves disturbances of both insulin and glucagon release. Studies on rodent islets have revealed the fundamental principles about how changes in plasma glucose levels stimulate or inhibit pancreatic islet hormone secretion. It is generally assumed ? without much justification - that data emanating from rodent studies can be extrapolated to man. The Human Islet Transplantation Centre in Oxford is one of two islet isolation centres in the UK. Via this centre we now have regular supply of high-quality human pancreatic islets. Over the last two years, we have characterized the electrophysiological and secretory characteristics of human beta-cells. We have found that human beta-cells differ from mouse beta-cells in a number of important ways. Collectively, the data obtained so far indicate that it is not possible to extrapolate rodent data to the situation in man. In order to understand the hormone secretion defects that associate with type-2 diabetes in man (rodent diabetes is a rare clinical disorder!), we require a much more detailed picture of the functional characteristics of human islet cells. This information should be highly relevant in the ongoing efforts developing new antidiabetic medicines.