The Response of a Non-Functional VIP- and Somatostatin-Containing Tumour to Tolbutamide in Vitro

Abstract
Woltering EA, O'Dorisio TM, Mekhjian HS, Ellison EC, Dyken T, Howe BA, Tuttle SE, Minton JP. The response of a non-functional VIP- and somatostatin-containing tumour to tolbutamide in vitro. A patient with a tumour containing clinically non-expressive somatostatin (SRIF) and vasoactive intestinal peptide (VIP) was studied in vivo with basal and tolbutamide-provoked SRIF and VIP measurements and failed to respond to tolbutamide infusion. An acute cell dispersion model was used to study this turnour after resection. Incubation of tumour cells in tolbutamide (2 mg/ml) resulted in increases in intra-cellular SRIF but not in the levels of SRIF released into the incubating medium. In contrast, incubation of tumour cells with tolbutamide decreased supernatant (extracellular) and total (intracellular) VIP by 50%, suggesting a local peptide-peptide modulation of VIP release by high intracellular levels of SRIF or, alternatively, suppression of VIP synthesis and/or release by tolbutamide. Failure of 'nonfunctional' tumours to produce symptoms or abnormal plasma peptide levels may be due to defects in peptide release or complex paracrine peptide-peptide interactions.