Oral Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Increases Circulating Endothelial Progenitor Cells in Patients With Type 2 Diabetes: Possible role of stromal-derived factor-1α

• Published in: Diabetes care Vol. 33; no. 7; pp. 1607 - 1609
• Main Authors: Fadini, Gian Paolo, Boscaro, Elisa, Albiero, Mattia, Menegazzo, Lisa, Frison, Vera, de Kreutzenberg, Saula, Agostini, Carlo, Tiengo, Antonio, Avogaro, Angelo
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.2010
• Subjects: Biological and medical sciences; chemokines; clinical trials; Diabetes. Impaired glucose tolerance; Dosage and administration; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelial growth factors; Endothelium; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Medical sciences; Metabolic diseases; metformin; Miscellaneous; nitrates; nitrites; noninsulin-dependent diabetes mellitus; Original Research; patients; Physiological aspects; Properties; Proteases; Public health. Hygiene; Public health. Hygiene-occupational medicine; Sitagliptin; stem cells; Type 2 diabetes; vascular endothelial growth factors; Italy; Dipeptidyl-peptidase IV; Endocrinopathy; Type 2 diabetes; Human; Endothelial cell; Nutrition; Enzyme; Stem cell; Oral administration; Enzyme inhibitor; Patient; Metabolic diseases; Sitagliptin; Increase; Peptidases; Hypoglycemic agent; Gliptine derivatives; Hydrolases; Dipeptidyl-peptidase IV inhibitor; Stromal derived factor 1α; Endocrinology
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc10-0187

OBJECTIVE: Vasculoprotective endothelial progenitor cells (EPCs) are regulated by stromal-derived factor-1α (SDF-1α) and are reduced in type 2 diabetes. Because SDF-1α 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. RESEARCH DESIGN AND 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-1α, 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-1α and a decrease in MCP-1. CONCLUSIONS: Sitagliptin increases circulating EPCs in type 2 diabetic patients with concomitant upregulation of SDF-1α. This ancillary effect of DPP-4 inhibition might have potential favorable cardiovascular implications.