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

In type 1 diabetes (T1D), there is a specific destruction of the insulin secreting pancreatic cell. Although the exact molecular mechanisms underlying 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 Ca2 concentration ([Ca2 ]i) and 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 cell are abolished in the presence of antibody against apoCIII. Increased serum levels of apoCIII can thus account for the increase in cell [Ca2 ]i and thereby cell apoptosis associated with T1D.