Apolipoprotein CIII promotes Ca2+-dependent β cell death in type 1 diabetes

Lisa Juntti-Berggren, Essam Refai, Ioulia Appelskog, Mats Andersson, Gabriela Imreh, Nancy Dekki, Sabine Uhles, Lina Yu, William J. Griffiths, Sergei Zaitsev, Ingo Leibiger, Shao Nian Yang, Gunilla Olivecrona, Hans Jörnvall, Per Olof Berggren

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

In type 1 diabetes (T1D), there is a specific destruction of the insulin secreting pancreatic β cell. Although the exact molecular mechanisms underlying β cell destruction are not known, sera from T1D patients have been shown to promote Ca2+-induced apoptosis. We now demonstrate that apolipoprotein CIII (apoCIII) is increased in serum from T1D patients and that this serum factor both induces increased cytoplasmic free intracellular Ca 2+ concentration ([Ca2+]i) and β cell death. The apoCIII-induced increase in [Ca2+]i reflects an activation of the voltage-gated L-type Ca2+ channel. Both the effects of T1D sera and apoCIII on the β cell are abolished in the presence of antibody against apoCIII. Increased serum levels of apoCIII can thus account for the increase in β cell [Ca2+]i and thereby β cell apoptosis associated with T1D.

Original languageEnglish (US)
Pages (from-to)10090-10094
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number27
DOIs
StatePublished - Jul 6 2004

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Apolipoprotein CIII promotes Ca<sup>2+</sup>-dependent β cell death in type 1 diabetes'. Together they form a unique fingerprint.

  • Cite this

    Juntti-Berggren, L., Refai, E., Appelskog, I., Andersson, M., Imreh, G., Dekki, N., Uhles, S., Yu, L., Griffiths, W. J., Zaitsev, S., Leibiger, I., Yang, S. N., Olivecrona, G., Jörnvall, H., & Berggren, P. O. (2004). Apolipoprotein CIII promotes Ca2+-dependent β cell death in type 1 diabetes. Proceedings of the National Academy of Sciences of the United States of America, 101(27), 10090-10094. https://doi.org/10.1073/pnas.0403551101