A low voltage-activated Ca2+ current mediates cytokine-induced pancreatic beta-cell death

Endocrinology. 1999 Mar;140(3):1200-4. doi: 10.1210/endo.140.3.6556.


Insulin-dependent diabetes mellitus is characterized by the selective destruction of pancreatic beta-cells. Chronic treatment with cytokines induced a low voltage-activated (LVA) Ca2+ current in mouse beta-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 beta-cell destruction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium Channels / physiology*
  • Cell Death / drug effects
  • Cell Line
  • Cytokines / pharmacology*
  • DNA Fragmentation
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / pathology
  • Mice
  • Patch-Clamp Techniques
  • Tumor Necrosis Factor-alpha / pharmacology


  • Calcium Channels
  • Cytokines
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma