title: The dipeptidyl peptidase-4 inhibitor sitagliptin suppresses mouse colon tumorigenesis in type 2 diabetic mice.
abstract: Patients with type 2 diabetes mellitus are known to have an increased risk of colorectal neoplasia. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been used as a new therapeutic tool for type 2 diabetes. Since the substrates for DPP-4 include intestinotrophic hormones and chemokines such as GLP-2 and stromal cell-derived factor-1 (SDF-1), which are associated with tumor progression, DPP-4 inhibitors may increase the risk of colorectal tumors. However, the influence of DPP-4 inhibitors on colorectal neoplasia in patients with type 2 diabetes remains unknown. In the present study, we show that long-term administration of a DPP-4 inhibitor, sitagliptin (STG), suppressed colon carcinogenesis in leptin-deficient (ob/ob) C57BL/6J mice. Colonic mucosal concentrations of glucagon‑like peptide-1 (GLP-1) and GLP-2 were significantly elevated in the ob/ob mice. However, mucosal GLP concentrations and the plasma level of SDF-1 were not affected by the administration of STG. Real‑time PCR analysis revealed that colonic mucosal IL-6 mRNA expression, which was significantly upregulated in the ob/ob mice, was significantly suppressed by the long-term administration of STG. These results suggest that a DPP-4 inhibitor may suppress colon carcinogenesis in mice with type 2 diabetes in a GLP-independent manner. Since DPP-4 has multiple biological functions, further studies analyzing other factors related to colon carcinogenesis are needed.
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 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, 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, 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, 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, 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, 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, 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, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, 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, 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, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000517:prevention & control; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D060888:Real-Time Polymerase Chain Reaction; D000068900:Sitagliptin Phosphate / Q000494:pharmacology*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D000068900:Sitagliptin Phosphate