Dynamics of insulin release by perifused insulin-producing tumoral cells: effects of glucose, forskolin, leucine, barium and theophylline.

Perifused tumoral insulin-producing cells, of the RINm5F line, display a high basal insulin output relative to their hormonal content. D-Glucose (2.8 or 16.7 mmol/l) causes a modest and monophasic increase in insulin output. The secretory response to D-glucose (1.4 to 16.7 mmol/l) is enhanced by forskolin, which exerts little effect in the absence of exogenous nutrient. L-Leucine (10.0 mmol/l) also stimulates insulin release from the perifused cells. The secretory response to these nutrient secretagogues in much less marked, however, than that evoked, in the absence of Ca2+, by the association of Ba2+ and theophylline. It is concluded that the dynamics of insulin release by the tumoral cells, when compared to that of normal islet cells, are characterized by several anomalies, including a high basal ratio between secretion and content, a low threshold (less than or equal to 1.4 mmol/l) in the secretory response to D-glucose, and a lesser responsiveness to nutrient than nonnutrient secretagogues.