GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE STIMULATED INSULIN RELEASE FROM A TUMOR-DERIVED BETA-CELL LINE (BETA-TC3)

The beta TC3 tumor cell line was examined for the presence of functional glucose-dependent insulinotropic polypeptide (GIP) receptors. Increasing amounts of natural porcine GIP decreased the binding of HPLC-purified [I-125]GIP to beta TC3 cells in a concentration-dependent manner. Displacement of GIP was significant at concentrations as low as 500 pM, and the radio-ligand was fully displaced at 100 nM. GIP((1-30)) produced a displacement of [I-125]GIP comparable with that produced by GIP((1.42)), and glucagon yielded 20% displacement at a concentration of 1 mu M but was without effect at 100 nM. Incubation of beta TC3 cells in the presence of glucose concentrations of 2-20 mM yielded a concentration-dependent stimulation of immunoreactive insulin (IRI) release. GIP and glucagon-like peptide-I-(7-36) amide (tGLP-I) at concentrations of 1 nM or greater significantly stimulated IRI release in the presence of 2 mM glucose. The threshold glucose concentration for GIP-stimulated IRI release from beta TC3 cells was 0.5 mM, and maximal potentiation of IRI release by GIP occurred at 5 mM glucose. Somatostatin significantly inhibited GIP-stimulated IRI release in the presence of 5 mM glucose. It is concluded that beta TC3 cells have functional GIP receptors and may provide a useful model for the study of IRI secretion at the cellular level.