Increased activity of L-type Ca2+ channels exposed to serum from patients with type I diabetes.
Type I diabetes [insulin-dependent diabetes mellitus (IDDM)] is an autoimmune disease associated with the destruction of pancreatic beta cells. Serum from patients with IDDM increased L-type calcium channel activity of insulin-producing cells and of GH3 cells derived from a pituitary tumor. The subsequent increase in the concentration of free cytoplasmic Ca2+ ([Ca2+]i) was associated with DNA fragmentation typical of programmed cell death or apoptosis. These effects of the serum were prevented by adding a blocker of voltage-activated L-type Ca2+ channels. When the serum was depleted of immunoglobulin M (IgM), it no longer affected [Ca2+]i. An IgM-mediated increase in Ca2+ influx may thus be part of the autoimmune reaction associated with IDDM and contribute to the destruction of beta cells in vivo.
Juntti-Berggren
L
L
Rolf Luft Center for Diabetes Research, Department of Endocrinology, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Larsson
O
O
Rorsman
P
P
Ammälä
C
C
Bokvist
K
K
Wåhlander
K
K
Nicotera
P
P
Dypbukt
J
J
Orrenius
S
S
Hallberg
A
A
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000502:physiology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D010911:Pituitary Neoplasms / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D015220:Calcium Channels; D007075:Immunoglobulin M; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D002118:Calcium