INSULIN-SECRETING CELL-LINES - CLASSIFICATION, CHARACTERISTICS AND POTENTIAL APPLICATIONS

The use of primary beta-cells in biochemical and molecular research is limited by the availability of pancreatic endocrine tissue. Numerous investigators have attempted to establish an insulin-secreting cell li ne that retains normal regulation of insulin secretion. Different appr oaches have been used, including induction of pancreatic tumours by ir radiation or viral infection, immortalization of beta-cells in vitro, and development of transgenic mice with targeted expression of a recom binant oncogene in the beta-cell. Few of these attempts have proven su ccessful, because cell differentiation and proliferation capacities ar e mutually exclusive. The most widely used insulin-secreting cell line s are RIN, HIT, beta TC, MIN6 and INS-1 cells. These cells contain mai nly insulin and small amounts of glucagon and somatostatin. RIN cells, except for the subclone RIN-38, are not glucose-responsive. HIT cells and beta TC cells secrete insulin in response to glucose, hut their d ose-response curve is markedly shifted to the left. MIN6, INS-1 and a newly available subclone of beta TC cells (beta TC-6 F7) are reported to retain normal regulation of glucose-induced insulin secretion. Alth ough the behaviour of none of these cell lines perfectly mimics primar y (b)eta-cell physiology, they are extremely valuable tools for the st udy of molecular events underlying beta-cell function and dysfunction. In addition, insulin-secreting cell lines represent a potential sourc e of transplantable tissue to overcome the limited availability of pri mary islets for this procedure.