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Cited by 336

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion

Fujino, Takahiro, Asaba, Hiroshi, Kang, Man-Jong, Ikeda, Yukio, Sone, Hideyuki, Takada, Shinji, Kim, Dong-Ho, Ioka, Ryoichi X., Ono, Masao, Tomoyori, Hiroko, Okubo, Minoru, Murase, Toshio, Kamataki, Akihisa, Yamamoto, Joji, Magoori, Kenta, Takahashi, Sadao, Miyamoto, Yoshiharu, Oishi, Hisashi, Nose, Masato, Okazaki, Mitsuyo, Usui, Shinichi, Imaizumi, Katsumi, Yanagisawa, Masashi, Sakai, Juro, Yamamoto, Tokuo T.·2003·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0133792100
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Abstract

A Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) plays an essential role in bone accrual and eye development. Here, we show that LRP5 is also required for normal cholesterol and glucose metabolism. The production of mice lacking LRP5 revealed that LRP5 deficiency led to increased plasma cholesterol levels in mice fed a high-fat diet, because of the decreased hepatic clearance of chylomicron remnants. In addition, when fed a normal diet, LRP5-deficient mice showed a markedly impaired glucose tolerance. The LRP5-deficient islets had a marked reduction in the levels of intracellular ATP and Ca 2+ in response to glucose, and thereby glucose-induced insulin secretion was decreased. The intracellular inositol 1,4,5-trisphosphate (IP3) production in response to glucose was also reduced in LRP5−/− islets. Real-time PCR analysis revealed a marked reduction of various transcripts for genes involved in glucose sensing in LRP5−/− islets. Furthermore, exposure of LRP5+/+ islets to Wnt-3a and Wnt-5a stimulates glucose-induced insulin secretion and this stimulation was blocked by the addition of a soluble form of Wnt receptor, secreted Frizzled-related protein-1. In contrast, LRP5-deficient islets lacked the Wnt-3a-stimulated insulin secretion. These data suggest that Wnt/LRP5 signaling contributes to the glucose-induced insulin secretion in the islets.

Overview

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Crossref · 10.1073/pnas.0133792100

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5 of 5 references verified0 citation errors · 0 not checkable

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Citations

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Research works printed but not linked: 34

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Metadata

Authors
Fujino, T., Asaba, H., Kang, M.-J., Ikeda, Y., Sone, H., Takada, S., Kim, D.-H., Ioka, R. X., Ono, M., Tomoyori, H., Okubo, M., Murase, T., Kamataki, A., Yamamoto, J., Magoori, K., Takahashi, S., Miyamoto, Y., Oishi, H., Nose, M., Okazaki, M., Usui, S., Imaizumi, K., Yanagisawa, M., Sakai, J., & Yamamoto, T. T.
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2002-12-30
Volume
100
Issue
1
Pages
229-234
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.0133792100
Cited by
336
References
5
Language
en

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