TNFa変換酵素を介したインスリン抵抗性発現機序の解析

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590987
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kumamoto University
• Principal Investigator: MOTOSHIMA Hiroyuki 熊本大学, 医学部附属病院, 助教 (40398201)
• Co-Investigator(Kenkyū-buntansha): MATSUMURA Takeshi 熊本大学, 医学部附属病院, 講師 (20398192) ; NISHIKAWA Takeshi 熊本大学, 生命科学研究部, 准教授 (70336212) ; KONDO Tatsuya 熊本大学, 生命科学研究部, 助教 (70398204)
• Project Period (FY): 2010 – 2012
• Keywords: 肥満 / 糖尿病 / インスリン抵抗性 / TNFa 変換酵素(TACE) / ストレスキナーゼ / インスリンシグナル伝達 / TNFa産生

Research Abstract

T umor necrosis factor (TNF) converting enzyme (TACE)cleaves the transmembrane precursor of TNF and produces mature TNF , which is aproinflammatory cytokine and one of the major mediators of obesity- and diabetes-inducedinsulin resistance. However , the regulation of TACE activity and expression ininsulin-sensitive tissues in obesity has not been fully determined. In the presentinvestigation, we found the adipose tissue-specific upregulation of TACE activity andexpression induced by obesity and the downregulation by caloric restriction in KKAy mice.In addition, we found that the activation of several stress-kinases may involve in theupreglation of TACE function in adipose tissue of obese mice.

Research Products

• [Journal Article] Apocynin suppresses theprogression of atherosclerosis inapoE-deficient mice by inactivationof macrophages (2013)
  • Author(s): Kinoshita H, Matsumura T, Ishii N,Fukuda K, Senokuchi T, Motoshima H,Kondo T, Taketa K, Kawasaki S,Hanatani S, Takeya M, Nishikawa T,Araki E
  • Journal Title: Biochem Biophys ResCommun Volume: 431 Pages: 124-30
  • Peer Reviewed
• [Journal Article] Regulation of TNFαconverting enzyme activity invisceral adipose tissue of obese mice (2013)
  • Author(s): Kawasaki S, Motoshima H, Hanatani S,Takaki Y, Igata M, Tsutsumi A,Matsumura T, Kondo T, Senokuchi T,Ishii N, Kinoshita H, Fukuda K,Kawashima J, Shimoda S, NishikawaT, Araki E
  • Journal Title: Biochem Biophys Res Commun Volume: 430 Pages: 1189-94
  • Peer Reviewed
• [Journal Article] Thiazolidinedione-independent activation of peroxisome proliferator activated receptor is a potential target for diabetic macrovascularcomplications (2012)
  • Author(s): Matsumura T, Taketa K, Shimoda S, ArakiE
  • Journal Title: J Diabetes Invest Volume: 3 Pages: 11-23
  • Peer Reviewed
• [Journal Article] Hyperthermia With MildElectrical Stimulation ProtectsPancreatic ss-Cells From Cell Stressesand Apoptosis (2012)
  • Author(s): Kondo T, Sasaki K, Matsuyama R,Morino-Koga S, Adachi H, Suico MA,Kawashima J, Motoshima H, Furukawa N,Kai H, Araki E
  • Journal Title: Diabetes Volume: 61 Pages: 837-847
  • Peer Reviewed
• [Journal Article] Pharmacotherapeutic Options for thePrevention of Cardiovascular Disease inPatients with Type 2 Diabetes (2012)
  • Author(s): Taketa K, Matsumura T, Furukawa N ArakiE
  • Journal Title: ClinicalMedicine Reviews in Vascular Health Volume: 4 Pages: 43-53
  • Peer Reviewed
• [Journal Article] Anti-atherosclerotic Potential ofDihydropyridine Calcium ChannelBlockers (2012)
  • Author(s): Ishii N, Matsumura T, Shimoda S, ArakiE
  • Journal Title: J Atheroscler Thromb Volume: 19 Pages: 693-704
  • Peer Reviewed
• [Journal Article] Caloricrestriction decreases ER stress inliver and adipose tissue in ob/ob mice (2011)
  • Author(s): Tsutsumi A, Motoshima H, Kondo T,Kawasaki S, Matsumura T, Hanatani S,Igata M, Ishii N, Kinoshita H, KawashimaJ, Taketa K, Furukawa N, Tsuruzoe K,Nishikawa T, Araki E
  • Journal Title: Biochem Biophys Res Commun Volume: 404 Pages: 339-344
  • Peer Reviewed
• [Journal Article] Glucose uptakein rat skeletal muscle L6 cells isincreased by low-intensity electricalcurrent through the activation of thephosphatidylinositol-3-OH kinase(PI-3K)/Akt pathway (2011)
  • Author(s): Yano S, Morino-Koga S, Kondo T, Suico MA,Koga T, Shimauchi Y, Matsuyama S, ShutoT, Sato T, Araki E, Kai H
  • Journal Title: J Pharmacol Sci Volume: 115 Pages: 94-98
  • Peer Reviewed
• [Journal Article] Telmisartan exerts antiatheroscleroticeffects by activating peroxisomeproliferator-activated receptor-r inmacrophages (2011)
  • Author(s): Matsumura T, Kinoshita H, Ishii N,Fukuda K, Motoshima H, Senokuchi T,Take ta K, Ka was aki S, N ish im aki- Mog ami T,Kawada T, Nishikawa T, Araki E
  • Journal Title: Arterioscler Thromb VascBiol Volume: 31 Pages: 1268-1275
  • Peer Reviewed
• [Journal Article] Angptl4 deficiencydecreases serum triglyceride levels in low-density lipoprotein receptorknockout mice and streptozotocin-induceddiabetic mice (2011)
  • Author(s): Adachi H, Kondo T, Koh GY, Nagy A, OikeY, Araki E
  • Journal Title: Biochem Biophys Res Commun Volume: 409 Pages: 177-180
  • Peer Reviewed
• [Journal Article] Heat shockresponse regulates insulin sensitivityand glucose homeostasis:pathophysiological impact andtherapeutic potential (2011)
  • Author(s): Kondo T, Koga S, Matsuyama R, MiyagawaK, Goto R, Kai H, Araki E
  • Journal Title: Curr DiabetesRev Volume: 7 Pages: 264-269
  • Peer Reviewed