To determine the control of the differentiated functions of the B- islet cells of the pancreas and to investigate the autoimmune etiology of insulin-dependent diabetes, well-characterized cell lines of defined genetic background are necessary. We have derived and characterized one such cell line from an insulinoma which arose in an SV40 T-antigen transgenic mouse. Based on our preliminary studies of the control of insulin release by these cells, we propose to address the interactions between nutrient and hormone that mediate insulin release. The IgSV195 cell line provides a particularly useful model to study the events which may lead to immune recognition of islet cell antigens. IgSV195 is derived from a tumor which arose in a genetically defined mouse strain, and these cells express SV40 T-antigen, a potent inducer of humoral and cellular immunity in the mouse. We propose to determine whether this antigen is spontaneously recognized by syngeneic mice bearing IgSV195 insulinomas or whether infection with the M strain of a EMC virus can induce its recognition by host lymphocytes. Finally, since the success of transfection experiments requires recipient cell line(s) of the same state of differentiation and preferably of the same species of origin as the genes to be tested, we plan to derive a cell line(s) from biopsies of human insulinomas. Each of these projects are designed as pilot studies to increase our expertise in the area, to accumulate data preparatory to a full grant application, and to determine the feasibility and relevance of these approaches to the study of diabetes.
| Gilligan, A; Jewett, L; Simon, D et al. (1989) Functional pancreatic beta-cell line from SV40 T-antigen transgenic mouse. Diabetes 38:1056-62 |
| Gilligan, A; Prentki, M; Glennon, C et al. (1988) Epidermal growth factor-induced increases in inositol trisphosphates, inositol tetrakisphosphates, and cytosolic Ca2+ in a human hepatocellular carcinoma-derived cell line. FEBS Lett 233:41-6 |
