title: 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.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yorifuji
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Iguchi
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Sakanaka
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Narabayashi
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kakimoto
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Sadaharu
authors.initials: S
authors.lastname: Nouda
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Okada
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Ishida
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Masuda
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Fukunishi
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Umegaki
authors.affiliation: Greater Los Angeles Veterans Affairs Healthcare System and School of Medicine, Department of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Yasutada
authors.initials: Y
authors.lastname: Akiba
authors.affiliation: Greater Los Angeles Veterans Affairs Healthcare System and School of Medicine, Department of Medicine, University of California, Los Angeles, California, USA ; Greater Los Angeles Veterans Affairs Healthcare System and School of Medicine, Department of Surgery, University of California, Los Angeles, California, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Kaunitz
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
keywords: DPP4; DPP8; GLP-1; GLP-2; sitagliptin