Physiological role of dehydroepiandrosterone

• Project/Area Number: 16K09806
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Kanagawa Dental College
• Principal Investigator: Aoki Kazutaka 神奈川歯科大学, 大学院歯学研究科, 教授 (60336542)
• Co-Investigator(Kenkyū-buntansha): 寺内 康夫 横浜市立大学, 医学研究科, 教授 (40359609)
• Research Collaborator: SATO haruhiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: DHEA / DHEA-S / 糖尿病 / インスリン感受性

Outline of Final Research Achievements

In an insulin tolerance test, dehydroepiandrosterone (DHEA) and DHEA-S administration decreased the initial plasma glucose levels in the db/db mice, but they did not decrease the ratios to the basal blood glucose level.
DHEA increased Akt phosphorylation in the liver of C57B6,insulin receptor substrate (IRS)1- and IRS2-deficient mice fed a high fat diet, suggesting that the increase in Akt signaling induced by DHEA is sufficient in the presence of IRS1 or IRS2. DHEA and DHEA-S did not increase Akt phosphorylation in the primary hepatocytes of C57B6 mice.

Academic Significance and Societal Importance of the Research Achievements

副腎アンドロゲンであるDHEAには抗糖尿病作用があるが、その詳細は不明であるため、マウスを用いて肝臓の糖代謝を中心に検討を行った。DHEAは、随時血糖値を改善させたが、インスリン低血糖試験では、インスリン感受性の改善を認めなかった。遺伝子欠損マウスを用いた検討で、DHEAは肝臓のインスリン感受性を亢進させ、これには少なくともIRS-1またはIRS-2のどちらかが存在すればよいことが明らかとなった。

Research Products

• [Journal Article] Usefulness of antidiabetic alpha-glucosidase inhibitors: a review on the timing of administration and effects on gut hormones (2019)
  • Author(s): Aoki Kazutaka、Sato Haruhiro、Terauchi Yasuo
  • Journal Title: Endocrine Journal Volume: 66 Issue: 5 Pages: 395-401
  • DOI: 10.1507/endocrj.EJ19-0041
  • NAID: 130007655246
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Switching From an Anti-Diabetic Loose Dose Combination to a Fixed Dose Combination Regimen at Equivalent Dosage for 6 Months on Glycemic Control in Japanese Patients With Type 2 Diabetes: A Pilot Study. (2017)
  • Author(s): Aoki K, Nagakura M, Taguri M, Kamiyama H, Masumura M, Furuie T, Oka M, Kamiko K, Nakajima S, Akema N, Terauchi Y
  • Journal Title: J Clin Med Res Volume: 9 Issue: 8 Pages: 719-724
  • DOI: 10.14740/jocmr3067w
  • Peer Reviewed / Open Access
• [Journal Article] Effect of eating speed on obesity and diabetes mellitus (Review) (2017)
  • Author(s): K Aoki, K Kamiko, H Kamiyama, H Sato, Y Terauchi
  • Journal Title: J Adv Nutr Hum Metab Volume: 3
  • DOI: 10.14800/janhm.1610
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of Plasma Glucose and Gut Hormone Levels Between Drinking Enteral Formula Over a Period of 5 and 20 Minutes in Japanese Patients With Type 2 Diabetes: A Pilot Study. (2016)
  • Author(s): Kamiko K, Aoki K, Kamiyama H, Taguri M, Terauchi Y.
  • Journal Title: J Clin Med Res. Volume: 8 Issue: 10 Pages: 749-752
  • DOI: 10.14740/jocmr2686w
  • Peer Reviewed / Open Access
• [Book] Vitamins and Hormones (2018)
  • Author(s): Aoki K, Terauchi Y.
  • Publisher: Elsevier Inc.
• [Book] Advances in Medicine and Biology Volume 114. (2017)
  • Author(s): Aoki K, Terauchi Y.
  • Publisher: Nova Science Publishers, Inc.