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

Kuwabara T, Kagalwala MN, Onuma Y, Ito Y, Warashina M, Terashima K, Sanosaka T, Nakashima K, Gage FH, Asashima M - EMBO Mol Med (2011)

Bottom Line: Paracrine Wnt3 plays an essential role in promoting the active expression of insulin in both hippocampal and OB-derived neural stem cells.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.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Science City, Japan. t.warashina@aist.go.jp

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Wnt3, released from pancreatic α cells, decreases in diabetesDetection of Wnt3 in the pancreatic α cells expressing GFAP. A confocal image of IHC of Wnt3 and GFAP in adult pancreatic islet is shown. Cells in the white square region are magnified and shown in separate panels at right. Wnt3, red; GFAP, green; DAPI, blue.Comparison of the number of Wnt3-positive cells in pancreas (left) and in DG of HPC (right) obtained from wild-type and diabetes rats. White bars, wild-type Fisher 344 rats (10-week old, male); grey bars, STZ-induced type I DB rats (10-week old, male); type II DB GK rats (10-week old, male). *p < 0.01 and **p < 0.001.Comparison of mRNA levels of Wnt3, insulin, IGFs and IGFBP-4 between wild-type and DB animals (STZ-induced DB rats) in the pancreas.Comparison of mRNA levels of Wnt3, insulin, IGFs and IGFBP-4 between wild-type and DB animals (STZ-induced DB rats) in the HPC. Relative levels of mRNA were normalized to GAPDH in the following Q-PCR analysis and are plotted at bottom.
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fig02: Wnt3, released from pancreatic α cells, decreases in diabetesDetection of Wnt3 in the pancreatic α cells expressing GFAP. A confocal image of IHC of Wnt3 and GFAP in adult pancreatic islet is shown. Cells in the white square region are magnified and shown in separate panels at right. Wnt3, red; GFAP, green; DAPI, blue.Comparison of the number of Wnt3-positive cells in pancreas (left) and in DG of HPC (right) obtained from wild-type and diabetes rats. White bars, wild-type Fisher 344 rats (10-week old, male); grey bars, STZ-induced type I DB rats (10-week old, male); type II DB GK rats (10-week old, male). *p < 0.01 and **p < 0.001.Comparison of mRNA levels of Wnt3, insulin, IGFs and IGFBP-4 between wild-type and DB animals (STZ-induced DB rats) in the pancreas.Comparison of mRNA levels of Wnt3, insulin, IGFs and IGFBP-4 between wild-type and DB animals (STZ-induced DB rats) in the HPC. Relative levels of mRNA were normalized to GAPDH in the following Q-PCR analysis and are plotted at bottom.

Mentions: Because neurons produced insulin (Fig 1), we were interested in the niches that supported neuronal differentiation. Astrocytes define the HPC niche (Song et al, 2002), and astrocyte-secreting Wnt3 factors (Fig S4A of Supporting information) have instructive effects in promoting adult neurogenesis (Lie et al, 2005). Glial fibrillary acidic protein (GFAP) is an astrocyte marker, and GFAP-expressing (GFAP+) cells were detected in pancreatic α cells (Fig S4B of Supporting information). Interestingly, IHC revealed that the pancreatic GFAP+ cells co-localized with Wnt3+ cells (Fig 2A), indicating that α cells release the neurogenic Wnt3 as do hippocampal astrocytes.


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

Kuwabara T, Kagalwala MN, Onuma Y, Ito Y, Warashina M, Terashima K, Sanosaka T, Nakashima K, Gage FH, Asashima M - EMBO Mol Med (2011)

Wnt3, released from pancreatic α cells, decreases in diabetesDetection of Wnt3 in the pancreatic α cells expressing GFAP. A confocal image of IHC of Wnt3 and GFAP in adult pancreatic islet is shown. Cells in the white square region are magnified and shown in separate panels at right. Wnt3, red; GFAP, green; DAPI, blue.Comparison of the number of Wnt3-positive cells in pancreas (left) and in DG of HPC (right) obtained from wild-type and diabetes rats. White bars, wild-type Fisher 344 rats (10-week old, male); grey bars, STZ-induced type I DB rats (10-week old, male); type II DB GK rats (10-week old, male). *p < 0.01 and **p < 0.001.Comparison of mRNA levels of Wnt3, insulin, IGFs and IGFBP-4 between wild-type and DB animals (STZ-induced DB rats) in the pancreas.Comparison of mRNA levels of Wnt3, insulin, IGFs and IGFBP-4 between wild-type and DB animals (STZ-induced DB rats) in the HPC. Relative levels of mRNA were normalized to GAPDH in the following Q-PCR analysis and are plotted at bottom.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3377118&req=5

fig02: Wnt3, released from pancreatic α cells, decreases in diabetesDetection of Wnt3 in the pancreatic α cells expressing GFAP. A confocal image of IHC of Wnt3 and GFAP in adult pancreatic islet is shown. Cells in the white square region are magnified and shown in separate panels at right. Wnt3, red; GFAP, green; DAPI, blue.Comparison of the number of Wnt3-positive cells in pancreas (left) and in DG of HPC (right) obtained from wild-type and diabetes rats. White bars, wild-type Fisher 344 rats (10-week old, male); grey bars, STZ-induced type I DB rats (10-week old, male); type II DB GK rats (10-week old, male). *p < 0.01 and **p < 0.001.Comparison of mRNA levels of Wnt3, insulin, IGFs and IGFBP-4 between wild-type and DB animals (STZ-induced DB rats) in the pancreas.Comparison of mRNA levels of Wnt3, insulin, IGFs and IGFBP-4 between wild-type and DB animals (STZ-induced DB rats) in the HPC. Relative levels of mRNA were normalized to GAPDH in the following Q-PCR analysis and are plotted at bottom.
Mentions: Because neurons produced insulin (Fig 1), we were interested in the niches that supported neuronal differentiation. Astrocytes define the HPC niche (Song et al, 2002), and astrocyte-secreting Wnt3 factors (Fig S4A of Supporting information) have instructive effects in promoting adult neurogenesis (Lie et al, 2005). Glial fibrillary acidic protein (GFAP) is an astrocyte marker, and GFAP-expressing (GFAP+) cells were detected in pancreatic α cells (Fig S4B of Supporting information). Interestingly, IHC revealed that the pancreatic GFAP+ cells co-localized with Wnt3+ cells (Fig 2A), indicating that α cells release the neurogenic Wnt3 as do hippocampal astrocytes.

Bottom Line: Paracrine Wnt3 plays an essential role in promoting the active expression of insulin in both hippocampal and OB-derived neural stem cells.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.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Science City, Japan. t.warashina@aist.go.jp

Show MeSH
Related in: MedlinePlus