Increased Activity of L-Type Ca$^{2+}$ 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 β cells. Serum from patients with IDDM increased L-type calcium channel activity of insulin-producing cells and of GH$_3$ cells derived from a pituitary tumor. The subsequent increase in the concentration of free cytoplasmic Ca$^{2+}$ ([Ca$^{2+}$]$_i$) 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 Ca$^{2+}$ channels. When the serum was depleted of immunoglobulin M (IgM), it no longer affected [Ca$^{2+}$]$_i$. An IgM-mediated increase in Ca$^{2+}$ influx may thus be part of the autoimmune reaction associated with IDDM and contribute to the destruction of β cells in vivo.