Identification of N-arachidonylglycine, U18666A, and 4-androstene-3,17- dione as novel insulin Secretagogues

Yukio Ikeda, Haruhisa Iguchi, Masanori Nakata, Ryoichi X. Ioka, Toshiya Tanaka, Satoshi Iwasaki, Kenta Magoori, Shinobu Takayasu, Tokuo T. Yamamoto, Tatsuhiko Kodama, Toshihiko Yada, Takeshi Sakurai, Masashi Yanagisawa, Juro Sakai

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


The glucose-induced insulin secretion is fine-tuned by numerous factors. To systematically identify insulinotropic factors, we optimized a primary β-cell-based functional assay to monitor intracellular Ca2+ flux ([Ca2+]i). By this assay system, we successfully identified several insulinotropic peptides including cholecystokinin, gastrin releasing peptide, vasopressin, and oxytocin from tissue extracts. Screening of an assortment of chemical compounds, we determined three novel insulin secretagogues: N-arachidonylglycine (NAGly), 3β-(2-diethylamino-ethoxy) androstenone hydrochloride (U18666A), and 4-androstene-3,17-dione. The NAGly increased [Ca2+]i through stimulation of the voltage-dependent Ca2+ channels and it was dependent on extracellular glucose level. On the other hand, U18666A and 4-androstene-3,17-dione increased [Ca2+]i in the presence of KATP channel opener diazoxide while it was inhibited by the presence of Ca2+ channel blocker nitrendipine, suggesting that their effects are independent of K ATP channel. These unique features will be useful for further development of insulinotropic factors and drugs for treating type 2 diabetes.

Original languageEnglish
Pages (from-to)778-786
Number of pages9
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 2005 Aug 5


  • Insulin secretion
  • Insulinotropic peptides
  • Intracellular calcium
  • Islet β-cells
  • Type 2 diabetes


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