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Article

The dipeptidyl peptidase-4 inhibitor sitagliptin suppresses mouse colon tumorigenesis in type 2 diabetic mice

  • Authors:
    • Naoki Yorifuji
    • Takuya Inoue
    • Munetaka Iguchi
    • Kaori Fujiwara
    • Kazuki Kakimoto
    • Sadaharu Nouda
    • Toshihiko Okada
    • Ken Kawakami
    • Yosuke Abe
    • Toshihisa Takeuchi
    • Kazuhide Higuchi
  • View Affiliations / Copyright

    Affiliations: Second Department of Internal Medicine, Osaka Medical College, Takatsuki City, Osaka 569-8686, Japan
  • Pages: 676-682
    |
    Published online on: November 16, 2015
       https://doi.org/10.3892/or.2015.4429
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Yorifuji N, Inoue T, Iguchi M, Fujiwara K, Kakimoto K, Nouda S, Okada T, Kawakami K, Abe Y, Takeuchi T, Takeuchi T, et al: The dipeptidyl peptidase-4 inhibitor sitagliptin suppresses mouse colon tumorigenesis in type 2 diabetic mice. Oncol Rep 35: 676-682, 2016.
APA
Yorifuji, N., Inoue, T., Iguchi, M., Fujiwara, K., Kakimoto, K., Nouda, S. ... Higuchi, K. (2016). The dipeptidyl peptidase-4 inhibitor sitagliptin suppresses mouse colon tumorigenesis in type 2 diabetic mice. Oncology Reports, 35, 676-682. https://doi.org/10.3892/or.2015.4429
MLA
Yorifuji, N., Inoue, T., Iguchi, M., Fujiwara, K., Kakimoto, K., Nouda, S., Okada, T., Kawakami, K., Abe, Y., Takeuchi, T., Higuchi, K."The dipeptidyl peptidase-4 inhibitor sitagliptin suppresses mouse colon tumorigenesis in type 2 diabetic mice". Oncology Reports 35.2 (2016): 676-682.
Chicago
Yorifuji, N., Inoue, T., Iguchi, M., Fujiwara, K., Kakimoto, K., Nouda, S., Okada, T., Kawakami, K., Abe, Y., Takeuchi, T., Higuchi, K."The dipeptidyl peptidase-4 inhibitor sitagliptin suppresses mouse colon tumorigenesis in type 2 diabetic mice". Oncology Reports 35, no. 2 (2016): 676-682. https://doi.org/10.3892/or.2015.4429
Copy and paste a formatted citation
x
Spandidos Publications style
Yorifuji N, Inoue T, Iguchi M, Fujiwara K, Kakimoto K, Nouda S, Okada T, Kawakami K, Abe Y, Takeuchi T, Takeuchi T, et al: The dipeptidyl peptidase-4 inhibitor sitagliptin suppresses mouse colon tumorigenesis in type 2 diabetic mice. Oncol Rep 35: 676-682, 2016.
APA
Yorifuji, N., Inoue, T., Iguchi, M., Fujiwara, K., Kakimoto, K., Nouda, S. ... Higuchi, K. (2016). The dipeptidyl peptidase-4 inhibitor sitagliptin suppresses mouse colon tumorigenesis in type 2 diabetic mice. Oncology Reports, 35, 676-682. https://doi.org/10.3892/or.2015.4429
MLA
Yorifuji, N., Inoue, T., Iguchi, M., Fujiwara, K., Kakimoto, K., Nouda, S., Okada, T., Kawakami, K., Abe, Y., Takeuchi, T., Higuchi, K."The dipeptidyl peptidase-4 inhibitor sitagliptin suppresses mouse colon tumorigenesis in type 2 diabetic mice". Oncology Reports 35.2 (2016): 676-682.
Chicago
Yorifuji, N., Inoue, T., Iguchi, M., Fujiwara, K., Kakimoto, K., Nouda, S., Okada, T., Kawakami, K., Abe, Y., Takeuchi, T., Higuchi, K."The dipeptidyl peptidase-4 inhibitor sitagliptin suppresses mouse colon tumorigenesis in type 2 diabetic mice". Oncology Reports 35, no. 2 (2016): 676-682. https://doi.org/10.3892/or.2015.4429
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