Regulation of adipocyte function by inhibitin of dipeptidyl peptidase-4
| Project/Area Number |
23591316
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Yokohama City University |
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Principal Investigator |
KIMURA Mari 横浜市立大学, 医学(系)研究科(研究院), 客員研究員 (40363840)
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| Co-Investigator(Kenkyū-buntansha) |
TERAUCHI Yasuo 横浜市立大学, 医学系研究科, 教授 (40359609)
NAKAMURA Akinobu 横浜市立大学, 医学研究科, 客員研究員 (70552420)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ジペプチジルペプチダーゼ-４ / 膵島 / マクロファージ / 遊離脂肪酸 / 内臓脂肪 / インクレチン / インスリン / ジペプチジルペプチダーゼ / ンスリン |
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| Research Abstract |
We investigated the extra-pancreatic effects of DPP-4 inhibition on visceral fat and the liver. The epididymal fat weight was significantly higher in beta-cell-specific glucokinase haploinsufficient (Gck+/-) mice fed a diet containing a combination of sucrose and linoleic acid (SL) than in mice fed a diet containing a combination of sucrose and oleic acid (SO). Compared with SO, SL increased the numbers of CD11c+ M1 macrophages and CD8+ T cells in visceral adipose tissue. DPP-4 inhibition significantly prevented adipose tissue infiltration by CD8+ T cells and M1 macrophages and decreased the expression of PAI-1. DPP-4 inhibition also prevented fatty liver in both wild-type mice and Gck+/- mice. DPP-4 inhibition also decreased the expressions of SREBP-1c, SCD-1 and FAS and increased the expression of PPARalpha in the liver. Thus, DPP-4 inhibition has extra-pancreatic protective effects against diet-induced adipose tissue inflammation and hepatic steatosis.
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Report
(4 results)
Research Products
(55 results)
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[Journal Article] Effects of the antitumor drug OSI-906, a dual inhibitor of IGF-1 receptor and insulin receptor, on the glycemic control,βcell functions, andβcell proliferation in male mice2014
Author(s)
Shirakawa J, Okuyama T, Yoshida E, Shimizu M, Horigome Y, Tuno T, Hayasaka M, Abe S, Fuse M, Togashi Y, Terauchi Y
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Journal Title
Endocrinology
Volume: (Epub ahead of print)
Related Report
Peer Reviewed
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[Journal Article] βcell proliferation after a partial pancreatectomy is independent of IRS-2 in mice2014
Author(s)
Togashi Y, Shirakawa J, Orime K, Kaji M, Sakamoto E, Tajima K, Inoue H, Nakamura A, Tochino Y, Goshima Y, Shimomura I, Terauchi Y
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Journal Title
Endocrinology
Volume: (Epub ahead of print)
Related Report
Peer Reviewed
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[Journal Article] β cell proliferation after a partial pancreatectomy is independent of IRS-2 in mice.2014
Author(s)
Togashi Y, Shirakawa J, Orime K, Kaji M, Sakamoto E, Tajima K, Inoue H, Nakamura A, Tochino Y, Goshima Y, Shimomura I, Terauchi Y.
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Journal Title
Endocrinology
Volume: 155
Issue: 5
Pages: 1643-52
DOI
Related Report
Peer Reviewed
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[Journal Article] Effects of the antitumor drug OSI-906, a dual inhibitor of IGF-1 receptor and insulin receptor, on the glycemic control, β cell functions, and β cell proliferation in male mice.2014
Author(s)
Shirakawa J, Okuyama T, Yoshida E, Shimizu M, Horigome Y, Tuno T, Hayasaka M, Abe S, Fuse M, Togashi Y, Terauchi Y.
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Journal Title
Endocrinology
Volume: 155
Related Report
Peer Reviewed
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[Journal Article] Metformin prevents liver tumorigenesis induced by high-fat diet in C57Bl/6 Mice2013
Author(s)
Tajima K, Nakamura A, Shirakawa J, Togashi Y, Orime K, Sato K, Inoue H, Kaji M, Sakamoto E, Ito Y, Aoki K, Nagashima Y, Atsumi T, Terauchi Y
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Journal Title
Am. J. Physiol. Endocrinol. Metab.
Volume: 305(8)
Related Report
Peer Reviewed
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[Journal Article] Metformin prevents liver tumorigenesis induced by high-fat diet in C57Bl/6 Mice.2013
Author(s)
Tajima K, Nakamura A, Shirakawa J, Togashi Y, Orime K, Sato K, Inoue H, Kaji M, Sakamoto E, Ito Y, Aoki K, Nagashima Y, Atsumi T, Terauchi Y.
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Journal Title
Am. J. Physiol. Endocrinol. Metab.
Volume: 305
Issue: 8
Pages: 987-998
DOI
Related Report
Peer Reviewed
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[Journal Article] Pleiotropic effects of sitagliptin in the treatment of type 2 diabetes mellitus patients2012
Author(s)
Kubota A, Maeda H, Kanamori A, Matoba K, Jin Y, Minagawa F, Obana M, Iemitsu K, Ito S, Amemiya H, Kaneshiro M, Takai M, Kaneshige H, Hoshino K, Ishikawa M, Minami N, Takuma T, Sasai N, Aoyagi S, Kawata T, Mokubo A, Takeda H, Honda S, Machimura H, Motomiya T, Waseda M, Naka Y, Tanaka Y, Terauchi Y, Matsuba I
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Journal Title
J Clin Med Res
Volume: 4(5)
Pages: 309-13
Related Report
Peer Reviewed
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[Journal Article] Impact of the dipeptidyl peptidase-4 inhibitor vildagliptin on glucose tolerance, beta cell function and mass in insulin receptor substrate-2-knockout mice fed a high-fat diet2012
Author(s)
Sato K, Nakamura A, Shirakawa J, Muraoka T, Togashi Y, Shinoda K, Orime K, Kubota N, Kadowaki T, Terauchi Y
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Journal Title
Endocrinology
Volume: 153(3)
Pages: 1093-102
Related Report
Peer Reviewed
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[Journal Article] Protective effect of a dipeptidyl peptidase-4 (DPP-4) inhibitor against increasedβcell apoptosis induced by dietary sucrose and linoleic acid in mice with diabetes2011
Author(s)
Shirakawa J, Amo K, Ohminami H, Orime K, Togashi Y, Ito Y, Tajima K, Koganei M, Sasaki H, Takeda E, Terauchi Y
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Journal Title
J Biol Chem
Volume: 286(29)
Pages: 25467-76
Related Report
Peer Reviewed
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[Journal Article] Diet-induced adipose tissue inflammation and liver steatosis are prevented by DPP-4 inhibition in diabetic mice2011
Author(s)
Shirakawa J, Fujii H, Ohnuma K, Sato K, Ito Y, Kaji M, Sakamoto E, Koganei M, Sasaki H, Nagashima Y, Amo K, Aoki K, Morimoto C, Takeda E and Terauchi Y
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Journal Title
Diabetes
Volume: 60
Pages: 1246-1257
Related Report
Peer Reviewed
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