The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1alpha.
OBJECTIVE
Vasculoprotective endothelial progenitor cells (EPCs) are regulated by stromal-derived factor-1alpha (SDF-1alpha) and are reduced in type 2 diabetes. Because SDF-1alpha is a substrate of dipeptidyl-peptidase-4 (DPP-4), we investigated whether the DPP-4 inhibitor sitagliptin modulates EPC levels in type 2 diabetic patients.


METHODS
This was a controlled, nonrandomized clinical trial comparing 4-week sitagliptin (n = 16) versus no additional treatment (n = 16) in addition to metformin and/or secretagogues in type 2 diabetic patients. We determined circulating EPC levels and plasma concentrations of SDF-1alpha, monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and nitrites/nitrates.


RESULTS
There was no difference in clinical baseline data between the sitagliptin and control arms. After 4 weeks, as compared with control subjects, patients receiving sitagliptin showed a significant increase in EPCs and SDF-1alpha and a decrease in MCP-1.


CONCLUSIONS
Sitagliptin increases circulating EPCs in type 2 diabetic patients with concomitant upregulation of SDF-1alpha. This ancillary effect of DPP-4 inhibition might have potential favorable cardiovascular implications.
Fadini
Gian Paolo
GP
Department of Clinical and Experimental Medicine, School of Medicine, University of Padova, Padova, Italy. gianpaolofadini@hotmail.com.
Boscaro
Elisa
E
Albiero
Mattia
M
Menegazzo
Lisa
L
Frison
Vera
V
de Kreutzenberg
Saula
S
Agostini
Carlo
C
Tiengo
Antonio
A
Avogaro
Angelo
A
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D054377:Chemokine CXCL12 / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D042783:Endothelial Cells / Q000166:cytology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D010865:Pilot Projects; D011719:Pyrazines / Q000008:administration & dosage*; D019718:Receptors, CXCR4 / Q000378:metabolism; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000008:administration & dosage*
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D011719:Pyrazines; D019718:Receptors, CXCR4; D014230:Triazoles; D008687:Metformin; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate