| Project/Area Number |
20591075
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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 |
Metabolomics
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
MIYAGAWA Jun-Ichiro Hyogo College of Medicine, 医学部, 教授 (00127721)
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| Co-Investigator(Kenkyū-buntansha) |
NAMBA Mitsuyoshi 兵庫医科大学, 医学部, 教授 (00183533)
HAMAGUCHI Tomoya 兵庫医科大学, 医学部, 講師 (60330461)
KATSUNO Tomoyuki 兵庫医科大学, 医学部, 助教 (30441257)
MIUCHI Masayuki 兵庫医科大学, 医学部, 助教 (90434951)
MURAI Kazuki 兵庫医科大学, 医学部, 助教 (40588373)
KONYA Hiroyuki 市立芦屋病院, 糖尿病内科, 部長 (50340956)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | インクレチン / 膵β細胞 / GLP-1(glucagon-like peptide-1) / 糖尿病 / L細胞 / 分化 / GLP-1 / 再生 / 消化管ホルモン |
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| Research Abstract |
Incretin hormone GLP-1(glucagon-like peptide-1) secreted from gastrointestinal tract has multi-potent physiological actions including increase or maintenance of beta cell mass (promotion of proliferation and neogenesis, and inhibition of apoptosis in beta cells). In addition to the incretin action, these effects that have not been demonstrated in human, are also important in view of regenerative medicine in diabetes mellitus.
We studied on the development and differentiation of GLP-1 secreting L cells in mice, and the change in the number of L cells in model mice of type 2 diabetes mellitus. In the intestinal tract, GLP-1-positive cells are difficult to detect in fetal period, and most of them appear in post-natal period, suggesting complicated mechanism for differentiation of L cells requiring endogenous and exogenous factors. Both in vivo and in vitro (GLP-1 secreting L cell line NCI-H716) studies, it was difficult and failed in detecting GLP-1-secretory factors (GLPSF) and L-cell proliferation factors (LCPF) suitable for the development of anti-diabetic drugs. In diabetic mice (db/db mice), relative L cell number appeared to be increased compared to that of control mice which showed the trend to decrease with aging.
In human study on the secretory response of incretin hormones (GIP and GLP-1) to oral glucose intake (75g OGTT) in Japanese subjects with normal glucose tolerance, both incretin hormones showed different actions to the change of plasma concentrations of glucose and insulin. The secretory response of GIP correlated positively to insulin secretion, while that of GLP-1 did not, and appeared to be involved at least in part in inhibition glucagon secretion.
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