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 language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Jul 6 2004|
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