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Requirement for the L-type Ca2+ channel α1D subunit in postnatal pancreatic β cell generation
Yoon Namkung, … , Sung-Sook Kim, Hee-Sup Shin
Yoon Namkung, … , Sung-Sook Kim, Hee-Sup Shin
Published October 1, 2001
Citation Information: J Clin Invest. 2001;108(7):1015-1022. https://doi.org/10.1172/JCI13310.
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Article

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

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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.

Authors

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

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Figure 2

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Serum insulin levels and glucose tolerance test. (a) Serum insulin conce...
Serum insulin levels and glucose tolerance test. (a) Serum insulin concentrations in nonfasting 10-week-old α1D–/– mice (open bar, n = 4) and control littermates (filled bar, n = 5). *P < 0.005. (b) Glucose tolerance tests of 12- to 14-week-old female mice. Blood glucose was determined at indicated time points after intraperitoneal glucose injection (2 mg/g body weight). Open circles, α1D–/– mice (n = 6); filled circles, wild-type littermates (n = 9). (c) Insulin tolerance tests were performed on fed animals. Results are expressed as percentage of initial blood glucose concentration. Open circles, α1D–/– mice (n = 7); filled circles, control littermates (n = 11). *P < 0.05; **P < 0.01.

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