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Publication

Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition.

Cell metabolism | 2019

Dipeptidyl peptidase-4 (DPP-4) controls glucose homeostasis through enzymatic termination of incretin action. We report that plasma DPP-4 activity correlates with body weight and fat mass, but not glucose control, in mice. Genetic disruption of adipocyte Dpp4 expression reduced plasma DPP-4 activity in older mice but did not perturb incretin levels or glucose homeostasis. Knockdown of hepatocyte Dpp4 completely abrogated the obesity-associated increase in plasma DPP-4 activity, reduced liver cytokine expression, and partially attenuated inflammation in adipose tissue without changes in incretin levels or glucose homeostasis. In contrast, circulating levels of soluble DPP4 (sDPP4) were dissociated from inflammation in mice with endothelial-selective or global genetic inactivation of Dpp4. Remarkably, inhibition of DPP-4 enzymatic activity upregulated circulating levels of sDPP4 originating from endothelial or hematopoietic cells without inducing systemic or localized inflammation. Collectively, these findings reveal unexpected complexity in regulation of soluble versus enzymatic DPP-4 and control of inflammation and glucose homeostasis.

Pubmed ID: 30393019 RIS Download

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Associated grants

Agency: CIHR, Canada

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This is a list of tools and resources that we have found mentioned in this publication.

CD 26, Dipeptidyl peptidase IV (DPPIV), (antibody)

RRID:AB_355739

This unknown targets Produced in goats immunized with purified, NS0-derived, recombinant mouse dipeptidyl peptidase IV (rmDPPIV) ectodomain

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F4/80 antibody [BM8] (antibody)

RRID:AB_443548

This monoclonal targets F4/80 antibody [BM8]

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B6.BKS(D)-Lepr^db/J (organism)

RRID:IMSR_JAX:000697

Mus musculus with name B6.BKS(D)-Lepr^db/J from IMSR.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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Quantity One 1-D Analysis Software (software resource)

RRID:SCR_014280

Software used for Bio-Rad imaging systems to acquire, quantitate, and analyze a variety of data. The software allows automatic configuration of imaging systems with appropriate filters, lasers, LEDs, and other illumination sources. It also contains tools for automated analysis of tests and assays such as 1-D electrophoretic gels, western blots, and colony counts.

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