Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb

被引:119
作者
Kuwabara, Tomoko [1 ]
Kagalwala, Mohamedi N. [2 ]
Onuma, Yasuko [1 ]
Ito, Yuzuru [1 ]
Warashina, Masaki [1 ]
Terashima, Kazuyuki [1 ]
Sanosaka, Tsukasa [3 ]
Nakashima, Kinichi [3 ]
Gage, Fred H. [2 ]
Asashima, Makoto [1 ]
机构
[1] Natl Inst Adv Ind Sci & Technol, Res Ctr Stem Cell Engn, Tsukuba, Japan
[2] Salk Inst Biol Studies, Genet Lab, La Jolla, CA USA
[3] Nara Inst Sci & Technol, Grad Sch Biol Sci, Lab Mol Neurosci, Takayama, Ikoma, Japan
关键词
diabetes; hippocampus; insulin; neural stem cell; olfactory bulb; NEURAL STEM-CELLS; BETA-CELLS; IGF-I; PANCREATIC DEVELOPMENT; TRANSGENIC MICE; DENTATE GYRUS; FETAL-BRAIN; DIFFERENTIATION; GROWTH; MULTIPOTENT;
D O I
10.1002/emmm.201100177
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
In the present study, we demonstrated that insulin is produced not only in the mammalian pancreas but also in adult neuronal cells derived from the hippocampus and olfactory bulb (OB). Paracrine Wnt3 plays an essential role in promoting the active expression of insulin in both hippocampal and OB-derived neural stem cells. Our analysis indicated that the balance between Wnt3, which triggers the expression of insulin via NeuroD1, and IGFBP-4, which inhibits the original Wnt3 action, is regulated depending on diabetic (DB) status. We also show that adult neural progenitors derived from DB animals retain the ability to give rise to insulin-producing cells and that grafting neuronal progenitors into the pancreas of DB animals reduces glucose levels. This study provides an example of a simple and direct use of adult stem cells from one organ to another, without introducing additional inductive genes.
引用
收藏
页码:742 / 754
页数:13
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