Publication
Title
Potential impact of sitagliptin on collagen-derived dipeptides in diabetic osteoporosis
Author
Abstract
It is known that diabetes coincides with an increased risk of osteoporosis. While a disturbed collagen metabolism is proposed as a possible cause, much remains unknown about the enzymes involved and changes in the collagen-derived dipeptides and amino acids. Therefore, we sought to study this intricate pathway and the effect of dipeptidyl peptidase 4 (DPP4) inhibitors. Control and streptozotocin-nicotinamide-induced diabetic rats were treated for 12 weeks with vehicle or sitagliptin, a DPP4 inhibitor (Con/VH, Con/SG, DM/VH and DM/SG). The activities of four key enzymes involved in collagen breakdown were determined in serum (DPP4, matrix metalloproteinase 2 and 9 and prolidase). Dipeptide (Ala-Pro, Gly-Pro, Pro-Pro and Pro-Hyp) and amino acid (Pro and Hyp) concentrations were measured by liquid chromatography coupled to mass spectrometry. We found three-fold higher MMP9 activities in DM/VH than in controls, while in DM/SG this rise was attenuated. MMP2 and prolidase did not differ in the investigated groups. Furthermore, we are the first to report on two-fold higher Ala-Pro and Pro-Pro levels in diabetes compared to controls. In contrast, Pro-Hyp concentrations were lower in diabetes (DM/VH and DM/SG). DPP4 inhibition does not seem to have a direct influence on the collagen metabolism in streptozotocin-nicotinamide-induced diabetic rats. Instead, it probably acts through its effect on osteoprotective substrates. In diabetes, increased MMP9 activities seem to favour the production of Ala-Pro and Pro-Pro containing collagen fragments. The high Pro-Hyp levels in untreated controls might have a bone-stimulating effect. Nevertheless, the biological significance of these dipeptides is not yet clear and should be further investigated.
Language
English
Source (journal)
Pharmacological research. - London
Publication
London : 2015
ISSN
1043-6618
Volume/pages
100(2015), p. 336-340
ISI
000363822600035
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 08.09.2015
Last edited 19.06.2017
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