Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2006) 11 P411

ECE2006 Poster Presentations Diabetes, metabolism and cardiovascular (174 abstracts)

The ways in which zinc enters beta cells in the pancreas and the influence of zinc blockers on the development of type 1 diabetes

Tsvia Priel , Michal Hershfinkel & Israel Sekler

Beb-Gurion University, Beer-Sheva, Israel.

Pancreatic islet beta cells contain a substantial amount of chelatable zinc (Zn2+), where it acts as a structural component of insulin packaging and is also co-secreted with insulin. Zinc at concentrations found in the pancreas is potentially harmful, and like in the brain, its permeation into endocrine cells may trigger the destruction of the islet leading to the onset of diabetes. Despite the potential importance little is known about the permeation pathways of zinc into beta cells.

In the present project, we have studied the influx pathways of zinc into the beta cell line Min6 and thereby possible mechanisms to lower intracellular zinc levels using single cell fluorescent imaging. We show that depolarization of cells is followed by massive influx of zinc, via the L-type Ca channels (LTCC) as indicated by the inhibition of this influx using the channel blocker nifedipein. Zinc influx persists in the presence of physiological concentrations of Ca2+, in contrast to Ca2+ is not pumped out. Indeed blocking of the LTCC prevents zinc induced cell death determined by LDH release. We have further determined the potential of a compound called Clioquinol (CQ) that can chelate intracellular zinc, to chelate the pancreatic pool of zinc and therefore to protect against zinc toxicity. Application of CQ had a protective effect and reduced zinc-induced cell death by 75%. Finally, in-vivo chelation of zinc protected against the onset of type 1 diabetes triggered by STZ. Thus our results indicate that the in vivo chelation of zinc may serve as therapeutic tool for the treatment of type 1 diabetes.

Volume 11

8th European Congress of Endocrinology incorporating the British Endocrine Societies

European Society of Endocrinology 
British Endocrine Societies 

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