Explore of a novel molecule regulating Langerhans cells by visualizing method

2016 Fiscal Year Annual Research Report

• Project/Area Number: 16K15495
• Research Institution: Kyoto University
• Principal Investigator: 中尾 一和 京都大学, 医学研究科, 特任教授 (00172263)
• Project Period (FY): 2016-04-01 – 2017-03-31
• Keywords: 膵ランゲルハンス島 / ゼブラフィッシュ / アルファ細胞 / ベータ細胞 / デルタ細胞 / 共焦点レーザー顕微鏡 / フローサイトメトリー / セルソーター

Outline of Annual Research Achievements

本研究では光学的に透明であるというゼブラフィッシュに対し、膵ランゲルハンス細胞の構成細胞であるα細胞、β細胞、δ細胞の各細胞に特異的な蛍光蛋白を発現する3重トランスジェニックゼブラフィッシュ（α細胞：gcgaプロモーター、mTurquoise、β細胞：insプロモーター、mCherry、δ細胞：sst2プロモーター、mVenus)を作成し解析することで生体のエネルギー代謝において特に重要な機能を持つ膵ランゲルハンス島細胞の量や比率の制御のための分子メカニズムに迫ろうとする試みである。膵ランゲルハンス島細胞の蛍光顕微鏡下の画像解析を5dpf(days post fertilization)、7dpf、9dpfにおこなった。これよりβ細胞数に対するα細胞数の割合は5dpfと比較して7dpf以降に急速に増加するということを明らかにした。さらに、5dpf、7dpf、9dpfの各時期における種々の膵島細胞の遺伝子発現を個別に検討するために、ゼブラフィッシュ膵島細胞のフローサイトメトリーによる解析およびセルソーターによる膵島細胞の採取に係る技術開発を行いこれに成功した。フローサイトメトリー及びセルソーターによるゼブラフィッシュの膵ランゲルハンス島細胞の解析は過去に報告はなく新規性が高い。今回の成果によって今後膵島細胞の正確な採取を行うことが可能となる。このことは従来検討が困難であった膵島内の細胞間相互作用・制御の分子メカニズムの解明につながる重要な技術であり、今後様々な関連する研究に寄与してゆくものである。

Research Products

• [Journal Article] MiR30-GALNT1/2 Axis-Mediated Glycosylation Contributes to the Increased Secretion of Inactive Human Prohormone for Brain Natriuretic Peptide (proBNP) From Failing Hearts. (2017)
  • Author(s): Nakagawa Y, Nishikimi T, Kuwahara K, Fujishima A, Oka S, Tsutamoto T, Kinoshita H, Nakao K, Cho K, Inazumi H, Okamoto H, Nishida M, Kato T, Fukushima H, Yamashita JK, Wijnen WJ, Creemers EE, Kangawa K, Minamino N, Nakao K, Kimura T
  • Journal Title: Journal of American Heart Association Volume: 6 Pages: e003601
  • DOI: 10.1161/JAHA.116.003601
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Endothelium-Derived C-Type Natriuretic Peptide Contributes to Blood Pressure Regulation by Maintaining Endothelial Integrity. (2017)
  • Author(s): Nakao K, Kuwahara K, Nishikimi T, Nakagawa Y, Kinoshita H, Minami T, Kuwabara Y, Yamada C, Yamada Y, Tokudome T, Nagai-Okatani C, Minamino N, Nakao YM, Yasuno S, Ueshima K, Sone M, Kimura T, Kangawa K, Nakao K
  • Journal Title: Hypertension Volume: 69 Pages: 286-296
  • DOI: 10.1161/HYPERTENSIONAHA.116.08219
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Role of leptin in conditioned place preference to high-fat diet in leptin-deficient ob/ob mice. (2017)
  • Author(s): Shimizu Y, Son C, Aotani D, Nomura H, Hikida T, Hosoda K, Nakao K
  • Journal Title: Neuroscience letter Volume: 640 Pages: 60-63
  • DOI: 10.1016/j.neulet.2017.01.033
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] MOB1-YAP1/TAZ-NKX2.1 axis controls bronchioalveolar cell differentiation, adhesion and tumour formation. Oncogene (2017)
  • Author(s): Otsubo K, Goto H, Nishio M, Kawamura K, Yanagi S, Nishie W, Sasaki T, Maehama T, Nishina H, Mimori K, Nakano T, Shimizu H, Mak TW, Nakao K, Nakanishi Y, Suzuki A
  • Journal Title: Oncogene Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1038/onc.2017.58
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Ablation of the N-type calcium channel ameliorates diabetic nephropathy with improved glycemic control and reduced blood pressure (2016)
  • Author(s): Ohno S, Yokoi H, Mori K, Kasahara M, Kuwahara K, Fujikura J, Naito M, Kuwabara T, Imamaki H, Ishii A, Saleem MA, Numata T, Mori Y, Nakao K, Yanagita M, Mukoyama M
  • Journal Title: Scientific Report Volume: 6 Pages: 27192
  • DOI: 10.1038/srep27192.2016
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Overall safety and efficacy of high-dose and low-dose intravenous glucocorticoid therapy in patients with moderate-to-severe active Graves' ophthalmopathy. (2016)
  • Author(s): Ueda-Sakane Y, Kanamoto N, Fushimi Y, Tanaka-Mizuno S, Yasuno S, Miura M, Sone M, Yasoda A, Okada T, Togashi K, Nakao K, Inagaki N
  • Journal Title: Endocrinology Jornal Volume: 63 Pages: 703-14
  • DOI: 10.1507/endocrj.EJ16-0038
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Brain-specific natriuretic peptide receptor-B deletion attenuates high-fat diet-induced visceral and hepatic lipid deposition in mice. (2016)
  • Author(s): Yamashita Y, Yamada-Goto N, Katsuura G, Ochi Y, Kanai Y, Miyazaki Y, Kuwahara K, Kanamoto N, Miura M, Yasoda A, Ohinata K, Inagaki N, Nakao K
  • Journal Title: Peptide Volume: 81 Pages: 38-50
  • DOI: 10.1016/j.peptides.2016.03.014
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] High incorporation of long-chain fatty acids contributes to the efficient production of acylated ghrelin in ghrelin-producing cells. (2016)
  • Author(s): Bando M, Iwakura H, Koyama H, Hosoda H, Shigematsu Y, Ariyasu H, Akamizu T, Kangawa K, Nakao K
  • Journal Title: FEBS Letter Volume: 590 Pages: 992-1001
  • DOI: 10.1002/1873-3468.12132
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Impaired adipogenic capacity in induced pluripotent stem cells from lipodystrophic patients with BSCL2 mutations. (2016)
  • Author(s): Mori E, Fujikura J, Noguchi M, Nakao K, Matsubara M, Sone M, Taura D, Kusakabe T, Ebihara K, Tanaka T, Hosoda K, Takahashi K, Asaka I, Inagaki N, Nakao K: Impaired adipogenic capacity in induced pluripotent stem cells from lipodystrophic patients with BSCL2 mutations.
  • Journal Title: Metabolism Volume: 62 Pages: 543-56
  • DOI: 10.1016/j.metabol.2015.12.015
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Establishment of Leptin-Responsive Cell Lines from Adult Mouse Hypothalamus (2016)
  • Author(s): Iwakura H, Dote K, Bando M, Koyama H, Hosoda K, Kangawa K, Nakao K
  • Journal Title: PLoS One Volume: 11 Pages: e0148639
  • DOI: 10.1371/journal.pone.0148639
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Reevaluation of anti-obesity action of mazindol and elucidation of its effect on the reward system. (2016)
  • Author(s): Aotani D, Son C, Shimizu Y, Nomura H, Hikida T, Kusakabe T, Tanaka T, Miyazawa T, Hosoda K, Nakao K
  • Journal Title: Neuroscience letter Volume: 633 Pages: 141-145
  • DOI: 10.1016/j.neulet.2016.09.014
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Book] Q&A 生活習慣病の科学 Neo －京都大学健康市民講座 (2016)
  • Author(s): 中尾一和
  • Total Pages: -
  • Publisher: 京都大学学術出版会
• [Book] Academic Press (2016)
  • Author(s): 錦見俊雄、桑原宏一郎、中川靖章、寒川賢治、中尾一和
  • Total Pages: -
  • Publisher: Endocrinology of the Heart in Health and Disease: Integrated, Cellular, and Molecular Endocrinology of the Heart