Requirement for the L-type Ca2+ channel alpha(1D) subunit in postnatal pancreatic beta cell generation

Pancreatic 5 cells are the source of insulin, which directly lowers blood g lucose levels in the body. Our analyses Of alpha (1D) gene-knockout (alpha (1D-/-)) mice show that the L-type calcium channel, alpha (1D), is required for proper beta cell generation in the postnatal pancreas. Knockout mice w ere characteristically slightly smaller than their littermates and exhibite d hypoinsulinemia and glucose intolerance. However, isolated a(1D)(-/-) isl ets persisted in glucose sensing and insulin secretion, with compensatory o verexpression of another L-type channel gene, alpha (1C). Histologically, n ewborn a(1D)(-/-) mice had an equivalent number of islets to wild-type mice . in contrast, adult alpha (-/-)(1D) mice showed a decrease in the number a nd size of islets, compared with littermate wild-type mice due to a decreas e in beta cell generation. TUNEL staining showed that there was no increase in cell. death in alpha (-/-)(1D) islets, and a 5-bromo-2 ' deoxyuridine-l abeling (BrdU-labeling) assay illustrated significant reduction in the prol iferation rate of beta cells in alpha (-/-)(1D) islets.