A cell line derived from intestinal tumors of transgenic mice (STC-1) was subcloned to produce a stable line with approximately 30% immunoreactive gastric inhibitory polypeptide (irGIP)-containing cells (STC 6-14). High-performance liquid chromatography (HPLC) of STC 6-14 extracts indicated that the tumor cell-derived irGIP had the same retention time as synthetic porcine GIP-(1-42) (pGIP). Approximately 30% of the cells also contained immunoreactive somatostatin (irSS), which eluted as a single peak on HPLC, corresponding with SS-(1-14). On average, each well of extracted cells (5.0 x 10(5) cultured 4 days) contained 33.3 +/- 1.4 ng irGIP and 18.4 +/- 1.5 ng irSS. Basal release of irGIP in the presence of 5 mM glucose was 733 +/- 58 pg.ml cells-1.2h-1 (2.20 +/- 0.17% of total cell content; TCC) and doubled at 20 mM glucose (4.20 +/- 0.42% TCC). The response to glucose was augmented by addition of a SS neutralizing antibody (SOMA-10) and suppressed by 10 nM SS. Basal release of irSS in 5 mM glucose was 377 +/- 35 pg.ml cells-1.2h-1 (2.05 +/- 0.19% TCC) and was increased by glucose (> or = 15 mM) and the addition of pGIP (> or = 1 nM). The STC 6-14 cell line represents a model to study the synthesis, storage, and release of GIP and SS in a controlled environment.