Apolipoprotein CIII promotes Ca super(2+)-dependent beta cell death in type 1 diabetes

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 27; pp. 10090 - 10094
• Main Authors: 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, Joernvall, H, Berggren, P-O
• Format: Journal Article
• Language: English
• Published: 06.07.2004
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0403551101

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