Zinc as a paracrine effector in pancreatic islet cell death.
Because of a huge amount of Zn2+ in secretory granules of pancreatic islet beta-cells, Zn2+ released in certain conditions might affect the function or survival of islet cells. We studied potential paracrine effects of endogenous Zn2+ on beta-cell death. Zn2+ induced insulinoma/islet cell death in a dose-dependent manner. Chelation of released endogenous Zn2+ by CaEDTA significantly decreased streptozotocin (STZ)-induced islet cell death in an in vitro culture system simulating in vivo circumstances but not in the conventional culture system. Zn2+ chelation in vivo by continuous CaEDTA infusion significantly decreased the incidence of diabetes after STZ administration. N-(6-methoxy-quinolyl)-para-toluene-sulfonamide staining revealed that Zn2+ was densely deposited in degenerating islet cells 24 h after STZ treatment, which was decreased by CaEDTA infusion. We show here that Zn2+ is not a passive element for insulin storage but an active participant in islet cell death in certain conditions, which in time might contribute to the development of diabetes in aged people.
Kim
B J
BJ
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kim
Y H
YH
Kim
S
S
Kim
J W
JW
Koh
J Y
JY
Oh
S H
SH
Lee
M K
MK
Kim
K W
KW
Lee
M S
MS
D001692:Biological Transport / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019899:Paracrine Communication / Q000502:physiology*; D013311:Streptozocin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
D002614:Chelating Agents; D013311:Streptozocin; D004492:Edetic Acid; D015032:Zinc