Physiological role of pancreatic incretin on the functional regulation of pancreatic islet cells
Project/Area Number |
26461350
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Metabolomics
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Research Institution | Kawasaki Medical School |
Principal Investigator |
Kaku Kohei 川崎医科大学, 医学部, 教授 (10116709)
|
Co-Investigator(Kenkyū-buntansha) |
下田 将司 川崎医科大学, 医学部, 講師 (60388957)
|
Research Collaborator |
NAKASHIMA Koji
KIMURA Tomohiko
HIRUKAWA Hidenori
OKAUCHI Seizo
OBATA Atsushi
KANETO Hideaki
SHIGETO Makoto
Rorsman Patrik
|
Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
Keywords | 糖尿病 / 膵ラ氏島機能 / 膵灌流 / 膵インクレチン / 膵α細胞 / GLP-1 / GLP-1受容体 / autocrine作用 / 膵GLP-1分泌 / 膵GLP-1受容体 / 膵ラ氏島GLP-1のautocrine機構 / 膵ラ氏島GLP-1のparacrine機構 / 糖尿病GKラット / 膵ラ氏島α細胞 / GLP-1産生細胞 / GLP-1R / GKラット / グルカゴン / インスリン / endosome |
Outline of Final Research Achievements |
To assess a physiological role of pancreatic GLP-1 on the regulation of pancreatic islet cell function, GLP-1 secretion by using pancreas perfusion study and GLP-1 receptors (GLP-1Rs) in islet cells by immunohistochemical analysis were investigated in non-diabetic and diabetic rats. The perfusion study of diabetic GK rats demonstrated a significant secretion of GLP-1 from the pancreas. GLP-1Rs were observed in α-cells in diabetic GK rats, but not in non-diabetic rats. Exendin-4 stimulated both glucagon and GLP-1 secretions from α-cells and cAMP-dependent insulin secretion from β-cells. In addition, the immunostochemical analysis revealed that GLP-1/GLP-1R complex induced the endosome formation in pancreatic α-cells of diabetic rats. These results strongly suggested the existence of autocrine mechanism of GLP-1/GLP-1R in pancreatic α-cells of diabetic rats, by which the deranged islet function in diabetic condition might be restored.
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Combination of DPP-4 inhibitor and PPARγ agonist exerts protective effects on pancreatic β-cells in diabetic db/db mice through the augmentation of IRS-2 expression.2015
Author(s)
Hirukawa H, Kaneto H, Shimoda M, Kimura T, Okauchi S, Obata A, Kohara K, Hamamoto S, Tawaramoto K, Hashiramoto M, Kaku K
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Journal Title
Mol Cell Endocrinol
Volume: 413
Pages: 49-60
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] GLP-1 stimulates insulin secretion by PKC-dependentTRPM4 and TRPM5 activation.2015
Author(s)
Shigeto M ,Ramracheya R, Tarasov AI, Cha C-Y, Chibalina MV, Hastoy B, Philippaert K, Reinbothe T, Rorsman N, Salehi A, Sones WR, Vergari E, Weston C, Gorelik J, Katsura M, Nikolaev VO, Vennekens R, Zaccolo M, Galione A, Johnson PVR, Kaku K, Ladds G, and Rorsman P
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Journal Title
J Clin Invest
Volume: 125
Issue: 12
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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