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 (HIT) 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 unstimulated cells. Ultrastructural analysis reveals that the secretory product of these cells is stored in membrane-bound granules that associate with microtubules under certain circumstances. Immunofluorescence studies using insulin antibody confirm the presence of insulin in granular structures in these cells. The microtubule inhibitor Nocodazole reduces the number of polymerized microtubules and inhibits the sustained phase of insulin secretion in HIT cells. Thus, the structural integrity of microtubules is important for the sustained phase of the insulin secretion to occur. The microtubule stabilizing drug taxol does not decrease insulin secretion. Since taxol blocks microtubule depolymerization, microtubule polymerization-depolymerization alone does not appear to be responsible for insulin granule transport. The increased use of these drugs in cancer research and therapy makes it important to understand their effects on insulin secretion.
Farshori
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Department of Zoology, University of Maryland, College Park 20742.
Goode
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D007516:Adenoma, Islet Cell / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D015739:Nocodazole / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured
D007328:Insulin; D005576:Colforsin; D005947:Glucose; D017239:Paclitaxel; D015739:Nocodazole