Apolipoprotein CIII promotes Ca2+-dependent beta cell death in type 1 diabetes.
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(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(2+) concentration ([Ca(2+)](i)) and beta cell death. The apoCIII-induced increase in [Ca(2+)](i) reflects an activation of the voltage-gated L-type Ca(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(2+)](i) and thereby beta cell apoptosis associated with T1D.
Juntti-Berggren
Lisa
L
Department of Molecular Medicine, Rolf Luft Center for Diabetes Research, Karolinska Institutet, SE-171 76 Stockholm, Sweden. lisa.juntti-berggren@molmed.ki.se
Refai
Essam
E
Appelskog
Ioulia
I
Andersson
Mats
M
Imreh
Gabriela
G
Dekki
Nancy
N
Uhles
Sabine
S
Yu
Lina
L
Griffiths
William J
WJ
Zaitsev
Sergei
S
Leibiger
Ingo
I
Yang
Shao-Nian
SN
Olivecrona
Gunilla
G
Jörnvall
Hans
H
Berggren
Per-Olof
PO
D000328:Adult; D000818:Animals; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000502:physiology*; D017209:Apoptosis; D002118:Calcium / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000473:pathology*; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000473:pathology*; D008297:Male; D051379:Mice
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D020746:Calcium Channels, L-Type; D002118:Calcium