title: Inhibitory effect of zinc on glucose-stimulated zinc/insulin secretion in an insulin-secreting β-cell line.
abstract: Diminished or inappropriate secretion of insulin is associated with type II diabetes. The cellular/molecular mechanism coupled with the regulation of insulin secretion is still under intense investigation. Divalent ion zinc (Zn(2+)) is co-packaged and co-secreted with insulin and is intimately involved in the process of insulin biosynthesis and the maturation of insulin secretory granules. The study reported here investigated glucose-stimulated zinc secretion (GSZS) and the effect of zinc on glucose-stimulated insulin secretion (GSIS) in the HIT-T15 pancreatic β-cell line. Zinc secretion was measured using a newly developed fluorescent zinc imaging approach, and the insulin secretion was measured using an enzyme-linked immunosorbent assay. There was apparent granular-like zinc staining in β-cells. The application of glucose induced detectable zinc secretion or GSZS. Like GSIS, GSZS was dependent on the glucose concentration (5-20 mm) and the presence of extracellular calcium. The application of a zinc chelator enhanced GSZS. When brief paired-pulse glucose stimulations, which involve the initial glucose stimulation followed by a second round of glucose stimulation, were applied, zinc secretion or GSZS that followed the first pulse was inhibited. This inhibition was reversed by zinc chelation, suggesting a feedback mechanism on GSZS by zinc secreted from β-cells. Finally, the application of zinc (50 μm) strongly inhibited GSIS as measured by enzyme-linked immunosorbent assay. The present study suggests that insulin secretion is regulated by co-secreted zinc that may act as an autocrine inhibitory modulator.
authors.affiliation: Department of Biomedical Sciences, Ohio University Heritage College of Osteopathic Medicine, Athens, OH 45701, USA.
authors.forename: Kira G
authors.initials: KG
authors.lastname: Slepchenko
authors.forename: Calvin B L
authors.initials: CB
authors.lastname: James
authors.forename: Yang V
authors.initials: YV
authors.lastname: Li
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D007328:Insulin; D005947:Glucose; D015032:Zinc; D002118:Calcium