Increased activity of L-type Ca2+ channels exposed to serum from patients with type I diabetes

Lisa Juntti-Berggren, Olof Larsson, Patrik Rorsman, Carina Ämmälä, Krister Bokvist, Karin Wåhlander, Pierluigi Nicotera, Jeanette Dypbukt, Sten Orrenius, Anders Hallberg, Per Olof Berggren

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Abstract

Type I diabetes [insulin-dependent diabetes mellitus (IDDM)] is an autoimmune disease associated with the destruction of pancreatic β cells. Serum from patients with IDDM increased L-type calcium channel activity of insulin-producing cells and of GH3 cells derived from a pituitary tumor. The subsequent increase in the concentration of free cytoplasmic Ca2+ ([Ca2+]i) was associated with DNA fragmentation typical of programmed cell death or apoptosis. These effects of the serum were prevented by adding a blocker of voltage-activated L-type Ca2+ channels. When the serum was depleted of immunoglobulin M (IgM), it no longer affected [Ca2+]i. An IgM-mediated increase in Ca2+ influx may thus be part of the autoimmune reaction associated with IDDM and contribute to the destruction of β cells in vivo.

Original languageEnglish (US)
Pages (from-to)86-90
Number of pages5
JournalScience
Volume261
Issue number5117
DOIs
StatePublished - Jan 1 1993

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    Juntti-Berggren, L., Larsson, O., Rorsman, P., Ämmälä, C., Bokvist, K., Wåhlander, K., Nicotera, P., Dypbukt, J., Orrenius, S., Hallberg, A., & Berggren, P. O. (1993). Increased activity of L-type Ca2+ channels exposed to serum from patients with type I diabetes. Science, 261(5117), 86-90. https://doi.org/10.1126/science.7686306