The Stimulus-secretion Coupling of Glucose-induced Insulin Release: V. The Participation of a Microtubular-microfilamentous System

The beta cell of the islets of Langerhans has been shown to contain a microtubular-microfilamentous system. The possible role of this system in the insulin secretory process was investigated by examining the effect upon glucoseinduced insulin secretion of mitotic spindle-inhibitors and microtubules-stabilizers. Inhibition of secretion was observed when the pieces of pancreas were pre-incubated for ninety minutes with either colchicine (0.01 to 1.0 mM) or vincristine (0.01 mM) prior to measurement of their secretory response to a high glucose concentration. Significant reduction of glucose-induced secretion was also noticed in thepresence of D₂O (25 per cent or more, v/v), 2-methyl-2,4-pentanediol (0.5 to 1.0 per cent, v/v) and ethanol (1.0 per cent, v/v). The inhibitory effect of D₂O was reversible. The stimulant action of glucose upon both calcium uptake and insulin biosynthesis by isolated islets was inhibited by mannoheptulose, but unaffected by either vincristine or D₂O, suggesting that the latter agents did not interfere with glucose metabolism in the beta cell. These results suggest that the integrity of the microtubular-microfilamentous system is required for glucose to exert its normal stimulant action upon insulin secretion. It is hypothesized that glucose-induced calcium uptake by the beta cell could trigger the release of insulin by causing the contraction of such system, favoring the migration of the secretory granules and their extrusion in the process of emiocytosis.