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

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.