Requirement for the L-type Ca²⁺ channel α_1D subunit in postnatal pancreatic β cell generation

Pancreatic β cells are the source of insulin, which directly lowers blood glucose levels in the body. Our analyses of α_1D gene-knockout (α_1D^-/-) mice show that the L-type calcium channel, α_1D, is required for proper β cell generation in the postnatal pancreas. Knockout mice were characteristically slightly smaller than their littermates and exhibited hypoinsulinemia and glucose intolerance. However, isolated α_1D^-/- islets persisted in glucose sensing and insulin secretion, with compensatory overexpression of another L-type channel gene, α_1C. Histologically, newborn α_1D^-/- mice had an equivalent number of islets to wild-type mice. In contrast, adult α_1D^-/- mice showed a decrease in the number and size of islets, compared with littermate wild-type mice due to a decrease in β cell generation. TUNEL staining showed that there was no increase in cell death in α_1D^-/- islets, and a 5-bromo-2′ deoxyuridine-labeling (BrdU-labeling) assay illustrated significant reduction in the proliferation rate of β cells in α_1D^-/- islets.