Effect of tissue specific insulin receptor knockout on whole body glucose oxidization

• Project/Area Number: 16K19529
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Tohoku University
• Principal Investigator: Takahashi Kei 東北大学, 医学系研究科, 助教 (00644808)
• Research Collaborator: SUGISAWA Takahashi 東北大学, 大学院医学系研究科, 大学院生
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 13Cーグルコース負荷試験 / 肝臓 / 骨格筋 / インスリン抵抗性 / 糖代謝異常 / 13C-グルコース呼気試験 / 糖尿病 / 内科 / 臨床

Outline of Final Research Achievements

13C-glucose breath test (13C-GBT) evaluates abundance of 13CO2 in exhaled air after oral administration of 13C-glucose, a glucose molecule labeled with stable isotope 13C. Through previous experiments, we found out that 13C-GBT can be used to determine whole body glucose oxidation in mice. The aim of the present study was to elucidate whether and how alteration of insulin actions in individual tissues affect whole body glucose oxidation. We generated inducible tissue specific insulin receptor knockout mice and administered them with 13C-glucose. We found that whole body glucose oxidation increases in these mice. These results suggest the existence of unspecified tissue that oxidizes great amount of glucose and thus produces large amount of CO2.

Research Products

• [Journal Article] Serum cystatin C level is associated with carotid arterial wall elasticity in subjects with type 2 diabetes mellitus: A potential marker of early-stage atherosclerosis. (2018)
  • Author(s): Kaneko R, Sawada S, Tokita A, Honkura R, Tamura N, Kodama S, Izumi T, Takahashi K, Uno K, Imai J, Yamada T, Miyachi Y, Hasegawa H, Kanai H, Ishigaki Y, Katagiri H
  • Journal Title: Diabetes Research and Clinical Practice Volume: 139 Pages: 43-51
  • DOI: 10.1016/j.diabres.2018.02.003
  • Peer Reviewed / Open Access
• [Journal Article] Olfactory receptors are expressed in pancreatic beta-cells and promote glucose-stimulated insulin secretion. (2018)
  • Author(s): Munakata Y, Yamada T, Imai J, Takahashi K, Tsukita S, Shirai Y, Kodama S, Asai Y, Sugisawa T, Chiba Y, Kaneko K, Uno K, Sawada S, Hatakeyama H, Kanzaki M, Miyazaki JI, Oka Y, Katagiri H
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 1499-1499
  • DOI: 10.1038/s41598-018-19765-5
  • Peer Reviewed / Open Access
• [Journal Article] Neuronal signals regulate obesity induced beta-cell proliferation by FoxM1 dependent mechanism. (2017)
  • Author(s): Yamamoto J, Imai J, Izumi T, Takahashi H, Kawana Y, Takahashi K, Kodama S, Kaneko K, Gao J, Uno K, Sawada S, Asano T, Kalinichenko VV, Susaki EA, Kanzaki M, Ueda HR, Ishigaki Y, Yamada T, Katagiri H
  • Journal Title: Nature Communications Volume: 8 Issue: 1 Pages: 1930-1930
  • DOI: 10.1038/s41467-017-01869-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Activation of Hypoxia Inducible Factor 1α Subunit Pathway in Steatotic Liver Contributes to Formation of Cholestrol Gallstones. (2017)
  • Author(s): Asai Y, Yamada T, Tsukita S, Takahashi K, Maekawa M, Honma M, Ikeda M, Murakami K, Munakata Y, Shirai Y, Kodama S, Sugisawa T, Chiba Y, Kondo Y, Kaneko K, Uno K, Sawada S, Imai J, Nakamura Y, Yamaguchi H, Tanaka K, Sasano H, Mano N, Ueno Y, Shimosegawa T, Katagiri H
  • Journal Title: Gastroenterology Volume: 印刷中 Issue: 6 Pages: 30012-4
  • DOI: 10.1053/j.gastro.2017.01.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ES Stress Protein CHOP Mediates Insulin Resistanse by Modulating Adipose Tissue Macrophage Polarity. (2017)
  • Author(s): Suzuki T, Gao J, Ishigaki Y, Kondo K, Sawada S, Izumi T, Uno K, Kaneko K, Tsukita S, Takahashi K, Asao A, Ishii N, Imai J, Yamada T, Oyadomarai S, Katagiri H
  • Journal Title: Cell Rep Volume: 18 Issue: 8 Pages: 2045-2057
  • DOI: 10.1016/j.celrep.2017.01.076
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNAs 106b and 222 Improve Hyperglycemia in a Mouse Model of Insulin-Deficient Diabetes via Pancreatic beta-Cell Proliferation. (2016)
  • Author(s): Tsukita S, Yamada T, Takahashi K, Munakata Y, Hosaka S, Takahashi H, Gao J, Shirai Y, Kodama S, Asai Y, Sugisawa T, Chiba Y, Kaneko K, Uno K, Sawada S, Imai J, Katagiri H
  • Journal Title: EBioMedicine Volume: 15 Pages: 163-172
  • DOI: 10.1016/j.ebiom.2016.12.002
  • Peer Reviewed / Open Access
• [Journal Article] 老化制御と代謝性疾患 (2016)
  • Author(s): 高橋圭、片桐秀樹
  • Journal Title: 日本臨床 Volume: 74 Pages: 1513-1517
• [Journal Article] 臓器関連と慢性炎症 (2016)
  • Author(s): 高橋圭、片桐秀樹
  • Journal Title: 最新醫學 Volume: 71 Pages: 2263-2268
• [Presentation] 肝臓と骨格筋のいずれでインスリン受容体を欠損させても全身におけるグルコース酸化はむしろ増加する (2018)
  • Author(s): 高橋圭、山田哲也、椙澤貴志、川田恵子、稲田睦、片桐秀樹
  • Organizer: 第29回分子糖尿病学シンポジウム
• [Presentation] 肝臓・骨格筋いずれでインスリン受容体を後天的に欠損させても全身におけるグルコース酸化はむしろ増加する (2018)
  • Author(s): 高橋圭、山田哲也、椙澤貴志、川田恵子、浅井洋一郎、宗像佑一郎、高橋広延、穂坂真一郎、清家準朗、児玉慎二郎、井泉知仁、高俊弘、宇野健司、澤田正二郎、今井淳太、稲田睦、片桐秀樹
  • Organizer: 第61回日本糖尿病学会年次学術集会