Combined treatment with dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin and elemental diets reduced indomethacin-induced intestinal injury in rats via the increase of mucosal glucagon-like peptide-2 concentration

• Fujiwara Kaori

  Second Department of Internal Medicine, Osaka Medical College

• Inoue Takuya

  Second Department of Internal Medicine, Osaka Medical College

• Yorifuji Naoki

  Second Department of Internal Medicine, Osaka Medical College

• Iguchi Munetaka

  Second Department of Internal Medicine, Osaka Medical College

• Sakanaka Taisuke

  Second Department of Internal Medicine, Osaka Medical College

• Narabayashi Ken

  Second Department of Internal Medicine, Osaka Medical College

• Kakimoto Kazuki

  Second Department of Internal Medicine, Osaka Medical College

• Nouda Sadaharu

  Second Department of Internal Medicine, Osaka Medical College

• Okada Toshihiko

  Second Department of Internal Medicine, Osaka Medical College

• Ishida Kumi

  Second Department of Internal Medicine, Osaka Medical College

• Abe Yosuke

  Second Department of Internal Medicine, Osaka Medical College

• Masuda Daisuke

  Second Department of Internal Medicine, Osaka Medical College

• Takeuchi Toshihisa

  Second Department of Internal Medicine, Osaka Medical College

• Fukunishi Shinya

  Second Department of Internal Medicine, Osaka Medical College

• Umegaki Eiji

  Second Department of Internal Medicine, Osaka Medical College

• Akiba Yasutada

  Greater Los Angeles Veterans Affairs Healthcare System and School of Medicine, Department of Medicine, University of California

• Kaunitz Jonathan D.

  Greater Los Angeles Veterans Affairs Healthcare System and School of Medicine, Department of Medicine, University of California Greater Los Angeles Veterans Affairs Healthcare System and School of Medicine, Department of Surgery, University of California

• Higuchi Kazuhide

  Second Department of Internal Medicine, Osaka Medical College

抄録

The gut incretin glucagon-like peptide-1 (GLP-1) and the intestinotropic hormone GLP-2 are released from enteroendocrine L cells in response to ingested nutrients. Treatment with an exogenous GLP-2 analogue increases intestinal villous mass and prevents intestinal injury. Since GLP-2 is rapidly degraded by dipeptidyl peptidase 4 (DPP4), DPP4 inhibition may be an effective treatment for intestinal ulcers. We measured mRNA expression and DPP enzymatic activity in intestinal segments. Mucosal DPP activity and GLP concentrations were measured after administration of the DPP4 inhibitor sitagliptin (STG). Small intestinal ulcers were induced by indomethacin (IM) injection. STG was given before IM treatment, or orally administered after IM treatment with or without an elemental diet (ED). DPP4 mRNA expression and enzymatic activity were high in the jejunum and ileum. STG dose-dependently suppressed ileal mucosal enzyme activity. Treatment with STG prior to IM reduced small intestinal ulcer scores. Combined treatment with STG and ED accelerated intestinal ulcer healing, accompanied by increased mucosal GLP-2 concentrations. The reduction of ulcers by ED and STG was reversed by co-administration of the GLP-2 receptor antagonist. DPP4 inhibition combined with luminal nutrients, which up-regulate mucosal concentrations of GLP-2, may be an effective therapy for the treatment of small intestinal ulcers.

収録刊行物

• Ｊｏｕｒｎａｌ　ｏｆ　Ｃｌｉｎｉｃａｌ　Ｂｉｏｃｈｅｍｉｓｔｒｙ　ａｎｄ　Ｎｕｔｒｉｔｉｏｎ

  Ｊｏｕｒｎａｌ　ｏｆ　Ｃｌｉｎｉｃａｌ　Ｂｉｏｃｈｅｍｉｓｔｒｙ　ａｎｄ　Ｎｕｔｒｉｔｉｏｎ 56 (2), 155-162, 2015

  一般社団法人　日本酸化ストレス学会

キーワード

• GLP-1
• GLP-2
• DPP4
• DPP8
• sitagliptin

詳細情報

• CRID: 1390001204674003584
• NII論文ID: 130004879376
• DOI: 10.3164/jcbn.14-111
• ISSN: 18805086
• ISSN: 09120009
• Web Site: https://search.jamas.or.jp/link/ui/2016045669
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可