EFFECTS OF THE MICROTUBULE DEPOLYMERIZING AND STABILIZING AGENTS NOCODAZOLE AND TAXOL ON GLUCOSE-INDUCED INSULIN-SECRETION FROM HAMSTER ISLET TUMOR (HIT) CELLS

Hamster islet tumor (KIT) cells retain much of the capacity of normal beta cells to act as glucose sensors. When stimulated with glucose or glucose plus forskolin, HIT cells release much more insulin than unsti mulated cells. Ultrastructural analysis reveals that the secretory pro duct of these cells is stored in membrane-bound granules that associat e with microtubules under certain circumstances. Immunofluorescence st udies using insulin antibody confirm the presence of insulin in granul ar structures in these cells. The microtubule inhibitor Nocodazole red uces the number of polymerized microtubules and inhibits the sustained phase of insulin secretion in HIT cells. Thus, the structural integri ty of microtubules is important for the sustained phase of the insulin secretion to occur. The microtubule stabilizing drug taxol does not d ecrease insulin secretion. Since taxol blocks microtubule depolymeriza tion, microtubule polymerization-depolymerization alone does not appea r to be responsible for insulin granule transport. The increased use o f these drugs in cancer research and therapy makes it important to und erstand their effects on insulin secretion.