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Endocrinology Vol. 140, No. 3 1200-1204
Copyright © 1999 by The Endocrine Society

ARTICLES

A Low Voltage-Activated Ca2+ Current Mediates Cytokine-Induced Pancreatic ß-Cell Death1

Lin Wang, Arin Bhattacharjee, Zhuang Zuo, Fuquan Hu, Richard E. Honkanen, Per-Olof Berggren and Ming Li

Departments of Pharmacology (L.W., A.B., F.H., M.L.) and Biochemistry (Z.Z., R.E.H.), University of South Alabama College of Medicine, Mobile, Alabama 36688; and The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institute (P.-O.B.), S-171 76 Stockholm, Sweden

Address all correspondence and requests for reprints to: Ming Li, Ph.D., Department of Pharmacology, University of South Alabama College of Medicine, Mobile, Alabama 36688. E-mail: mli{at}jaguar1.usouthal.edu

Insulin-dependent diabetes mellitus is characterized by the selective destruction of pancreatic ß-cells. Chronic treatment with cytokines induced a low voltage-activated (LVA) Ca2+ current in mouse ß-cells. The concomitant increase in the basal cytoplasmic free Ca2+ concentration ([Ca2+]i) was associated with DNA fragmentation and cell death. Antagonists of LVA Ca2+ channels prevented this elevation of basal [Ca2+]i and DNA fragmentation and reduced the percentage of cell death. Exposure to cytokines did not affect the profile of Ca2+ currents or basal [Ca2+]i in glucagon-secreting {alpha}-cells. An increased Ca2+ signal through LVA Ca2+ channels may thus be a key feature in cytokine-induced ß-cell destruction.




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