| Project/Area Number |
18590703
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
SAITOH Toshihito Tokyo Women's Medical University, Dept. Internal Medicin, Associate Professor (50246609)
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| Co-Investigator(Kenkyū-buntansha) |
OTSUKA Hiroko Tokyo Women's Medical University, Dept. Intanal Medicin, Assistant Professor (20307606)
TAKAHASHI Haruki Tokyo Women's Medical University, Dept. Intanal Medicin, Assistant Professor (00246612)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | gastric acid secretion / double knock out / histamine H2 receptor / gastrin receptor / gastric mucosa |
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| Research Abstract |
We have conducted the experiments to examine the effect of deficiency of histamine H2 receptor on differentiation and proliferation of gastric mucosa in histamine H2 receptor knock out mouse. We have generated a double knock out mouse which expresses phenotype of deficiencies both H2 and gastrin receptors after intercrossing of each line. This double knock out is useful for investigating the mechanism of gastric acid secretion and the influence on differentiation and proliferation of gastric mucosa. We investigated histological changes in gastric mucosa and alteration of lipid and glucose metabolism in double knock out mouse comparing with wild type mouse. Gastric acid secretion was decreased in double knock out phenotype. Gastric pH monitoring revealed constant higher values in double knock phenotype comparing with wild type. Histological change in cytoarchitecture of gastric mucosa was recognized in double knock out mice. There was no difference in survival time between double knock out and wild phenotype. Mean body weight in double knock out mice was higher than that of wild type mice under the same caloric intake. The levels of blood sugar and neutral lipids were also higher in knock out mice. The activity of PI3 kinase, which is related to hypertrophy of muscle, liver and fat calls, was slightly increased in double knock out mice. It is well known that the decrease of gastric acid secretion and the elevation of gastric pH play important roles in pathomechanism of gastric acid relater disorders, such as reflux esophagitis, pepsic ulcer and duodenal ulcer. Our present studies suggest that the elevation of gastric pH leads to changes of structure of gastric mucosa, which may affect not only digestion and absorption in GI tract, but glucose and lipids metabolism in whole bodies.
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