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Inhibitory effect of zinc on glucose‐stimulated zinc/insulin secretion in an insulin‐secreting β‐cell line
Author(s) -
Slepchenko Kira G.,
James Calvin B. L.,
Li Yang V.
Publication year - 2013
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2013.072348
Subject(s) - zinc , insulin , secretion , medicine , endocrinology , extracellular , biology , autocrine signalling , stimulation , chemistry , biochemistry , receptor , organic chemistry
New Findings• What is the central question of this study? The main aim of the present study was to determine glucose‐stimulated zinc secretion and the effect of zinc on glucose‐stimulated insulin secretion in pancreatic β‐cells. • What is the main finding and its importance? Using a newly developed approach, we demonstrated a robust glucose‐stimulated zinc secretion. Importantly, the application of zinc inhibited glucose‐stimulated insulin secretion. Our findings provide evidence that zinc, after being secreted, can regulate the insulin secretion of β‐cells by a negative feedback mechanism.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 m m ) 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 μ m ) 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.