Dipeptidyl peptidase 4 has been a central research topic of the Laboratory of Medical Biochemistry for many years. Our research group has a top international reputation in this field.
DPP4 as a therapeutic target in ischemia/reperfusion injury
Dipeptidyl peptidase 4 (DPP4, DPPIV, CD26, EC 18.104.22.168) was discovered more than four decades ago as a serine protease that cleaves off N-terminal dipeptides from peptide substrates.
Pharmacological inhibition of DPP4 activity ameliorates glucose tolerance in type 2 diabetes patients by prolonging the half-life of the incretin glucagon-like peptide-1 (GLP-1). This results in an increased insulin secretion.
Apart from glucose homeostasis, DPP4 is involved in other (patho)physiological processes. As the current indication of DPP4 inhibitors –type 2 diabetes- typically implies long-term treatment of patients, a more profound understanding of the effects of chronic DPP4 inhibition on peptide metabolism becomes very important.
In preclinical models, DPP4 inhibitors have the ability to protect the heart, kidneys and lung against injury induced by an ischemic insult followed by reperfusion (ischemia/reperfusion injury, IRI). Via collaborative research we are involved in IRI related experiments(1)(2).
We are currently optimizing assays to quantify the in vivo levels of truncated versus non-truncated peptide substrates of DPP4, as these are needed to further clarify the involvement of each of these substrates. More specifically, our endeavors aim to differentially detect and quantify SDF-1α (CXCL12) versus desLys-Pro-SDF-1α and BNP vs desSer-Pro-BNP, by mass spectrometry.
For a full account of DPP4 as a therapeutic target in IRI, we recommend “Matheeussen et al.” (3)
- Glorie, L. L. F., Verhulst, A., Matheeussen, V., Baerts, L., Magielse, J., Hermans, N., D’Haese, P. C., De Meester, I., and De Beuf, A. (2012) American journal of physiology. Renal physiology 303, F681–8
- Jungraithmayr, W., De Meester, I., Matheeussen, V., Baerts, L., Arni, S., and Weder, W. (2012) European journal of cardio-thoracic surgery 41, 1166–73
- Matheeussen, V., Jungraithmayr, W., and De Meester, I. (2012) Pharmacology & therapeutics 136, 267–82