NDLI: Combining MK626, a Novel DPP-4 Inhibitor, and Low-Dose Monoclonal CD3 Antibody for Stable Remission of New-Onset Diabetes in Mice

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Combining MK626, a Novel DPP-4 Inhibitor, and Low-Dose Monoclonal CD3 Antibody for Stable Remission of New-Onset Diabetes in Mice

Content Provider	Semantic Scholar
Author	Ding, Lei Gysemans, Conny A. Stangé, Geert M. Heremans, Yves Yuchi, Yixing Takiishi, Tatiana Korf, Hannelie Chintinne, Marie Carr, Richard D. Heimberg, Harry Pipeleers, Daniel G. Mathieu, Chantal
Copyright Year	2014
Abstract	Combining immune intervention with therapies that directly influence the functional state of the β-cells is an interesting strategy in type 1 diabetes cure. Dipeptidyl peptidase-4 (DPP-4) inhibitors elevate circulating levels of active incretins, which have been reported to enhance insulin secretion and synthesis, can support β-cell survival and possibly stimulate β-cell proliferation and neogenesis. In the current study, we demonstrate that the DPP-4 inhibitor MK626, which has appropriate pharmacokinetics in mice, preceded by a short-course of low-dose anti-CD3 generated durable diabetes remission in new-onset diabetic non-obese diabetic (NOD) mice. Induction of remission involved recovery of β-cell secretory function with resolution of destructive insulitis and preservation of β-cell volume/mass, along with repair of the islet angioarchitecture via SDF-1- and VEGF-dependent actions. Combination therapy temporarily reduced the CD4-to-CD8 distribution in spleen although not in pancreatic draining lymph nodes (PLN) and increased the proportion of effector/memory T cells as did anti-CD3 alone. In contrast, only combination therapy amplified Foxp3+ regulatory T cells in PLN and locally in pancreas. These findings open new opportunities for the treatment of new-onset type 1 diabetes by introducing DPP-4 inhibitors in human CD3-directed clinical trials.
File Format	PDF HTM / HTML
DOI	10.1371/journal.pone.0107935
PubMed reference number	25268801
Journal	Medline
Volume Number	9
Alternate Webpage(s)	https://cris.vub.be/files/27259713/Ding_et_al_PlosONE_2014.pdf
Alternate Webpage(s)	https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0107935&type=printable
Journal	PloS one
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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