title: Apolipoprotein CIII promotes Ca2+-dependent beta cell death in type 1 diabetes.
abstract: 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.
authors.affiliation: Department of Molecular Medicine, Rolf Luft Center for Diabetes Research, Karolinska Institutet, SE-171 76 Stockholm, Sweden. lisa.juntti-berggren@molmed.ki.se
authors.forename: Lisa
authors.initials: L
authors.lastname: Juntti-Berggren
authors.forename: Essam
authors.initials: E
authors.lastname: Refai
authors.forename: Ioulia
authors.initials: I
authors.lastname: Appelskog
authors.forename: Mats
authors.initials: M
authors.lastname: Andersson
authors.forename: Gabriela
authors.initials: G
authors.lastname: Imreh
authors.forename: Nancy
authors.initials: N
authors.lastname: Dekki
authors.forename: Sabine
authors.initials: S
authors.lastname: Uhles
authors.forename: Lina
authors.initials: L
authors.lastname: Yu
authors.forename: William J
authors.initials: WJ
authors.lastname: Griffiths
authors.forename: Sergei
authors.initials: S
authors.lastname: Zaitsev
authors.forename: Ingo
authors.initials: I
authors.lastname: Leibiger
authors.forename: Shao-Nian
authors.initials: SN
authors.lastname: Yang
authors.forename: Gunilla
authors.initials: G
authors.lastname: Olivecrona
authors.forename: Hans
authors.initials: H
authors.lastname: Jörnvall
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
mesh_terms: 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
chemical_list: D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D020746:Calcium Channels, L-Type; D002118:Calcium