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Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans.

Publication ,  Journal Article
Baggio, LL; Varin, EM; Koehler, JA; Cao, X; Lokhnygina, Y; Stevens, SR; Holman, RR; Drucker, DJ
Published in: Nat Commun
July 28, 2020

Dipeptidyl peptidase-4 (DPP4) modulates inflammation by enzymatic cleavage of immunoregulatory peptides and through its soluble form (sDPP4) that directly engages immune cells. Here we examine whether reduction of DPP4 activity alters inflammation. Prolonged DPP4 inhibition increases plasma levels of sDPP4, and induces sDPP4 expression in lymphocyte-enriched organs in mice. Bone marrow transplantation experiments identify hematopoietic cells as the predominant source of plasma sDPP4 following catalytic DPP4 inhibition. Surprisingly, systemic DPP4 inhibition increases plasma levels of inflammatory markers in regular chow-fed but not in high fat-fed mice. Plasma levels of sDPP4 and biomarkers of inflammation are lower in metformin-treated subjects with type 2 diabetes (T2D) and cardiovascular disease, yet exhibit considerable inter-individual variation. Sitagliptin therapy for 12 months reduces DPP4 activity yet does not increase markers of inflammation or levels of sDPP4. Collectively our findings dissociate levels of DPP4 enzyme activity, sDPP4 and biomarkers of inflammation in mice and humans.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

July 28, 2020

Volume

11

Issue

1

Start / End Page

3766

Location

England

Related Subject Headings

  • Sitagliptin Phosphate
  • Protein Isoforms
  • Middle Aged
  • Mice, Knockout
  • Mice
  • Metformin
  • Male
  • Inflammation Mediators
  • Inflammation
  • Humans
 

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Baggio, L. L., Varin, E. M., Koehler, J. A., Cao, X., Lokhnygina, Y., Stevens, S. R., … Drucker, D. J. (2020). Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans. Nat Commun, 11(1), 3766. https://doi.org/10.1038/s41467-020-17556-z
Baggio, Laurie L., Elodie M. Varin, Jacqueline A. Koehler, Xiemin Cao, Yuliya Lokhnygina, Susanna R. Stevens, Rury R. Holman, and Daniel J. Drucker. “Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans.Nat Commun 11, no. 1 (July 28, 2020): 3766. https://doi.org/10.1038/s41467-020-17556-z.
Baggio LL, Varin EM, Koehler JA, Cao X, Lokhnygina Y, Stevens SR, et al. Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans. Nat Commun. 2020 Jul 28;11(1):3766.
Baggio, Laurie L., et al. “Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans.Nat Commun, vol. 11, no. 1, July 2020, p. 3766. Pubmed, doi:10.1038/s41467-020-17556-z.
Baggio LL, Varin EM, Koehler JA, Cao X, Lokhnygina Y, Stevens SR, Holman RR, Drucker DJ. Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans. Nat Commun. 2020 Jul 28;11(1):3766.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

July 28, 2020

Volume

11

Issue

1

Start / End Page

3766

Location

England

Related Subject Headings

  • Sitagliptin Phosphate
  • Protein Isoforms
  • Middle Aged
  • Mice, Knockout
  • Mice
  • Metformin
  • Male
  • Inflammation Mediators
  • Inflammation
  • Humans