Insulin gene regulation and islet development as studied in genetically modified tumors and transgenic laboratory animals

Abstract

The pancreatic islet of Langerhans is composed of four highly distinct cell types specialized to mass produce a particular hormone. Insulin is thus the main product released from the islet B—cell in response to elevated glucose.The four cell types maturate during fetal development. Pluripotent rat islet tumors can to a certain degree undergo similar maturation processes when passaged in vivo. Such a model has been used to study the B—cell specific process of insulin gene activation. Transgenic mice have been instrumental in defining the functional regulatory elements involved in restricting the insulin gene activity to the pancreatic B-cell. The tissue-specific enhancer/promoter has thus been identified and used in combination with a series of other genes which in transgenic mice targets expression of the gene in question selectively to the B-cell. Important transacting factors have been identified and cloned which are in part responsible for mediating tissue specific insulin gene expression. One such factor when "knocked-out" results in a phenotype lacking the entire pancreas. Future developments in targeting "knockout" of genes to particular cell types will help dissecting out the multiple functions of such regulatory transacting factors.