Chapter 2. Marketed Small Molecule Dipeptidyl Peptidase IV (DPP4) Inhibitors as a New Class of Oral Anti-Diabetics

Pei, Zhonghua

doi:10.1039/9781849735322-00015

Cited by 1 publication

(1 citation statement)

References 47 publications

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“…Consistent with this, the expression of the DPP-IV protease is reduced in certain cancer types (e.g., human lung SCC). Because DPP-IV inhibitors are currently used to treat human type II diabetes (50,51), their potential long-term impact on the balance between cell growth and apoptosis in this niche warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Signaling-active IGF-1 by Dipeptidyl Peptidase IV (DPP-IV)

Chen,

Tang,

Han

et al. 2010

Int. J Biomed Sci.

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Functioning as an extracellular protease, dipeptidyl peptidase IV (DPP-IV) preferentially cleaves the peptide bond after the penultimate proline residue. We report here that DPP-IV cleaves the first two amino acids from insulin-like growth factor 1 (IGF-1), revealed by mass spectrometry. The kinetic parameters of the proteolytic cleavage indicate that this reaction is physiologically relevant. Interestingly, truncated IGF-1 is less potent than the full-length protein in activating the IGF-1R, but binds more readily to IGF-binding protein 3 (IGFBP3). Quantitative RT-PCR showed that the level of DPP-IV mRNA is dramatically lower in lung squamous cell carcinoma tissues than in adjacent nonneoplastic lung tissues. However, this reduction was not observed in lung adenocarcinoma tissues. Our study suggests a possible link between IGF-1 and DPP-IV in cancer development in a specific tumor niche. A DPP-IV-related pathway may be important in mitigating IGF-1 signaling. Consequently, a robust IGF signaling pathway may accelerate early carcinogenesis in environments lacking DPP-IV.

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Section: Discussionmentioning

confidence: 99%