Potential impact of sitagliptin on collagen-derived dipeptides in diabetic osteoporosis

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Lesley BaertsIngrid De Meester

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 ...Continue Reading

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