Binding of sperm and oocyte induced by gut factor: Novel strategy for treatment of male infertility

• Project/Area Number: 25670692
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Akita University
• Principal Investigator: YAMADA Yuichiro 秋田大学, 医学(系)研究科(研究院), 教授 (60283610)
• Co-Investigator(Kenkyū-buntansha): TERADA Yukihiro 秋田大学, 大学院医学系研究科, 教授 (10260431)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: インクレチン / 不妊

Outline of Final Research Achievements

GIP, which is secreted from endocrine K cells of small intestine, not only stimulates insulin secretion from pancreatic beta-cells but also exerts various extra-pancreatic effects. We have shown that GIP receptors are highly expressed in testis, knockout of GIP receptor leads to decreased artificial fertilization, and expression of factor X is decreased in testis of GIP receptor KO mice and high fat-fed mice, that factor X may be involved in binding of sperm and oocytes. These results suggests that GIP signaling and factor X are participated in male infertility induced by high fat or over-eating.

Research Products

• [Journal Article] Effects of miglitol, sitagliptin, and initial combination therapy with both on plasma incretins’ responses to a mixed meal and visceral fat in over-weight Japanese patients with type 2 diabetes. “The MASTER randomized, controlled trial” (2014)
  • Author(s): Mikada A, Narita T, Yokoyama H, Yamashita R, Horikawa Y, Tsukiyama K, Yamada Y
  • Journal Title: Diabetes Res Clin Pract Volume: 106 Issue: 3 Pages: 538-547
  • DOI: 10.1016/j.diabres.2014.09.040
  • Peer Reviewed
• [Journal Article] Dipeptidyl peptidase 4 (DPP-4) is expressed in mouse and human islets and its activity is decreased in human islets from individuals with type 2 diabetes. (2014)
  • Author(s): Omar BA, Liehua L, Yamada Y, Seino Y, Marchetti P, Ahrén B
  • Journal Title: Diabetologia Volume: 57 Issue: 9 Pages: 1876-1883
  • DOI: 10.1007/s00125-014-3299-4
  • Peer Reviewed
• [Journal Article] High saturated fatty acid intake induces insulin secretion by elevating gastric inhibitory polypeptide levels in healthy individuals (2014)
  • Author(s): Itoh K., Moriguchi R., Yamada Y., Fujita M., Yamato T., Oumi M., Holst JJ., Seino Y.
  • Journal Title: Nutrition Research Volume: 34 Issue: 8 Pages: 653-660
  • DOI: 10.1016/j.nutres.2014.07.013
  • Peer Reviewed
• [Journal Article] Sensory and motor physiological functions are impaired in gastric inhibitory polypeptide receptor deficient mice. (2014)
  • Author(s): Okawa T, Kamiya H, Himeno T, Kato J, Seino Yus, Fukami A, Fujiya A, Kondo M, Tsunekawa S, Naruse K, Hamada Y, Hayashi Y, Harada N, Yamada Y, Inagaki N, Seino Yut, Oiso Y, Nakamura J
  • Journal Title: J Diabetes Invest Volume: 5 Pages: 31-37
  • Peer Reviewed
• [Journal Article] The protective roles of GLP-1R signaling in diabetic nephropathy: possible mechanism and therapeutic potential (2014)
  • Author(s): Fujita H, Morii T, Fujishima H, Sato T, Shimizu T, Hosoba M, Tsukiyama K, Narita T, Takahashi T, Drucker DJ, Seino Y, Yamada Y
  • Journal Title: Kidney Int Volume: 85 Issue: 3 Pages: 579-589
  • DOI: 10.1038/ki.2013.427
  • Peer Reviewed
• [Journal Article] DPP-4 inhibition with alogliptin on top of anigiotensin II type 1 receptor blockage ameliorates albuminuria via up-regulation of SDF-1a in type 2 diabetic patients with incipient nephropathy (2014)
  • Author(s): Fujita H, Taniai H, Murayama H, Ohshiro H, Sato S, Kikuchi N, Komatsu T, Komatsu Ko, Komatsu Ka, Narita T, Yamada Y
  • Journal Title: Endocr J Volume: 61 Pages: 159-66
  • Peer Reviewed
• [Journal Article] Effects of consumption of main and side dishes with white rice on postprandial glucose, insulin, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 responses in healthy Japanese men. (2014)
  • Author(s): Kameyama N, Maruyama C, Matsui S, Araki R, Yamada Y, Maruyama T
  • Journal Title: Br J Nutr Volume: 111 Issue: 9 Pages: 1632-40
  • DOI: 10.1017/s0007114513004194
  • Peer Reviewed
• [Journal Article] A quantitative analytical method for determining the levels of gastric inhibitory polypeptides GIP1-42 and GIP3-42 in human plasma using LC-MS/MS/MS. (2013)
  • Author(s): Miyachi A, Murase T, Yamada Y, Osonoi T, Harada KI
  • Journal Title: J Proteome Res Volume: 12 Issue: 6 Pages: 2690-99
  • DOI: 10.1021/pr400069f
  • Peer Reviewed
• [Presentation] 177 精巣におけるGIPシグナルの低下は肥満・糖尿病における男性不妊をおこす (2014)
  • Author(s): 清水辰徳、月山克史、佐藤雄大、藤田浩樹、成田琢磨、寺田幸弘、山田祐一郎
  • Organizer: 第87回日本内分泌学会学術集会
  • Place of Presentation: 福岡国際会議場