Apolipoprotein CIII promotes Ca&sup2+; -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 Ca2+ 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. [ABSTRACT FROM AUTHOR]