Pathophysiological roles of monocyte insulin signaling and NF-kBactivation in diabetes

2012 Fiscal Year Final Research Report

• Project/Area Number: 23791038
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Kumamoto University
• Principal Investigator: SENOKUCHI Takafumi 熊本大学, 大学院・生命科学研究部, 特任助教 (00530320)
• Co-Investigator(Renkei-kenkyūsha): MATSUMURA Takeshi 熊本大学, 大学院・生命科学研究部, 助教 (20398192)
• Project Period (FY): 2011 – 2012
• Keywords: メタボリックシンドローム

Research Abstract

In this study we investigate the implication of monocyte/macrophage inflammation andproliferation in diabetes progression. Macrophage and monocyte cultured in high glucoseshowed activated inflammatory activity, and pulsate stimulation with high glucose inducedsignificantly increased inflammatory cytokine expression. Along with the increase ofinflammatory activity, the cell cycle inhibitor, p27kip expression was increased, andmacrophage proliferation was inhibited in high glucose culture. On the other hand, themacrophage specific p27kip transgenic mouse, whose macrophage proliferation is inhibited,showed improved glucose tolerance after high fat diet loading. Further studies arenecessary to reveal the pathophysiological roles of monocyte/macrophage inflammation andproliferation in the progression of diabetes.

Research Products

• [Journal Article] Apocynin suppresses the progression ofatherosclerosis in apoE-deficient mice by inactivation of macrophages (2013)
  • Author(s): Kinoshita H, Matsumura T, Ishii N,Fukuda K, Senokuchi T, Motoshima H,Kondo T, Taketa K, Kawasaki S, HanataniS, Takeya M, Nishikawa T, Araki E
  • Journal Title: BiochemBiophys Res Commun Volume: 431(2) Pages: 124-130
  • DOI: DOI: 10.1016/j.bbrc.2013.01.014.
  • Peer Reviewed
• [Journal Article] Regulation of TNFα converting enzymeactivity in visceral adipose tissue ofobese mice (2012)
  • Author(s): Kawasaki S, Motoshima H, Hanatani S,Takaki Y, Igata M, Tsutsumi A, MatsumuraT, Kondo T, Senokuchi T, Ishii N,Kinoshita H, Fukuda K, Kawashima J,Shimoda S, Nishikawa T, Araki E
  • Journal Title: Biochem Biophys Res Commun Volume: 430(4) Pages: 1189-1194
  • DOI: DOI:10.1016/j.bbrc.2012.12.086.
  • Peer Reviewed
• [Journal Article] Novel function of transthyretin inpancreatic alpha cells (2012)
  • Author(s): Su Y, Jono H, Misumi Y, Senokuchi T, GuoJ, Ueda M, Shinriki S, Tasaki M, ShonoM, Obayashi K, Yamagata K, Araki E, AndoY
  • Journal Title: FEBS Lett Volume: 586(23) Pages: 4215-4222
  • DOI: DOI:10.1016/j.febslet.2012.10.025.
  • Peer Reviewed
• [Journal Article] The occurrence ofislet amyloid polypeptide amyloidosisin Japanese subjects (2012)
  • Author(s): Su Y, Misumi Y, Ueda M, Shono M, TasakiM, Guo J, Jono H, Obayashi K, SenokuchiT, Yamagata K, Ando Y
  • Journal Title: Pancreas Volume: 41(6) Pages: 971-973
  • DOI: DOI:10.1097/MPA.0b013e318249926a.
  • Peer Reviewed
• [Journal Article] Telmisartan exerts antiatherosclerotic effects by activatingPPARγ in macrophages Arterioscler (2011)
  • Author(s): Matsumura T, Kinoshita H, Ishii N,Fukuda K, Motoshima H, Senokuchi T,Taketa K, Kawasaki S, Nishimaki-MogamiT, Kawada T, Nishikawa T, Araki E
  • Journal Title: Thromb Vasc Biol Volume: 31(6) Pages: 1268-1275
  • DOI: DOI:10.1161/ATVBAHA.110.222067.
  • Peer Reviewed
• [Journal Article] Voltage-gated K(+) channelKCNQ1 regulates insulin secretion inMIN6 β-cell line (2011)
  • Author(s): Yamagata K, Senokuchi T, Lu M, TakemotoM, Fazlul Karim M, Go C, Sato Y, HattaM, Yoshizawa T, Araki E, Miyazaki J,Song WJ
  • Journal Title: Biochem Biophys ResCommun Volume: 407(3) Pages: 620-625
  • DOI: DOI:10.1016/j.bbrc.2011.03.083.
  • Peer Reviewed
• [Journal Article] Mitochondrial dysfunction andincreased reactive oxygen speciesimpair insulin secretion insphingomyelin synthase 1 null mice (2011)
  • Author(s): Yano M, Watanabe K, Yamamoto T, Ikeda K,Senokuchi T, Lu M, Kadomatsu T, TsukanoH, Ikawa M, Okabe M, Yamaoka S, OkazakiT, Umehara H, Gotoh T, Song WJ, Node K,Taguchi R, Yamagata K, Oike Y
  • Journal Title: JBiol Chem Volume: 286(5) Pages: 3992-4002
  • DOI: DOI:10.1074/jbc.M110.179176.
  • Peer Reviewed
• [Presentation] 20 歳代で発症した GAD 抗体陰性、IA-2抗体陽性 緩徐進行 1 型糖尿病の 1 例 (2012)
  • Author(s): 瀬ノ口 隆文、竹田 佳代、河島 淳司、下田 誠也、佐藤 美紀、荒木 栄一
  • Organizer: 第50回日本糖尿病学会九州地方会
  • Place of Presentation: ホテルマリターレ創世 久留米
  • Year and Date: 2012-10-19
• [Presentation] NAD 依存性脱アセチル化酵素 SIRT7 の糖代謝への関与の検討 (2011)
  • Author(s): 瀬ノ口 隆文、郷 知佐、吉澤 達也、宮田 敬士、Eva Bober、尾池 雄一、荒木 栄一、山縣 和也
  • Organizer: 第54回 日本糖尿病学会年次学術集会
  • Place of Presentation: 国際館パミール 札幌
  • Year and Date: 2011-05-19