Requirement for the L-type Ca2+ channel α1D subunit in postnatal pancreatic β cell generation

Yoon Namkung, Nataliya Skrypnyk, Myung Jin Jeong, Taehoon Lee, Myung Shik Lee, Hyung Lae Kim, Hemin Chin, Pann Ghill Suh, Sung Sook Kim, Hee Sup Shin

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

Pancreatic β cells are the source of insulin, which directly lowers blood glucose levels in the body. Our analyses of α1D gene-knockout (α1D-/-) mice show that the L-type calcium channel, α1D, 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 α1D-/- islets persisted in glucose sensing and insulin secretion, with compensatory overexpression of another L-type channel gene, α1C. Histologically, newborn α1D-/- mice had an equivalent number of islets to wild-type mice. In contrast, adult α1D-/- 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 α1D-/- islets, and a 5-bromo-2′ deoxyuridine-labeling (BrdU-labeling) assay illustrated significant reduction in the proliferation rate of β cells in α1D-/- islets.

Original languageEnglish
Pages (from-to)1015-1022
Number of pages8
JournalJournal of Clinical Investigation
Volume108
Issue number7
DOIs
StatePublished - 2001

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