title: Sitagliptin, a dipeptidyl peptidase-4 inhibitor, increases the number of circulating CD34⁺CXCR4⁺ cells in patients with type 2 diabetes.
abstract: We investigated the effects of sitagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, on the number of circulating CD34(+)CXCR4(+)cells, a candidate for endothelial progenitor cells (EPCs), plasma levels of stromal cell-derived factor (SDF)-1α, a ligand for CXCR4 receptor and a substrate for DPP-4, and plasma levels of interferon-inducible protein (IP)-10, for a substrate for DPP-4, in patients with type 2 diabetes. We studied 30 consecutive patients with type 2 diabetes who had poor glycemic control despite treatment with metformin and/or sulfonylurea. Thirty diabetic patients were randomized in a 2:1 ratio into a sitagliptin (50 mg/day) treatment group or an active placebo group (glimepiride 1 mg/day) for 12 weeks. Both groups showed similar improvements in glycemic control. The number of circulating CD34(+)CXCR4(+) cells was increased from 30.5 (20.0, 47.0)/10(6) cells at baseline to 55.5 (31.5, 80.5)/10(6) cells at 12 weeks of treatment with 50 mg/day sitagliptin (P = 0.0014), while showing no significant changes in patients treated with glimepiride. Plasma levels of SDF-1α and IP-10, both physiological substrates of endogenous DPP-4 and chemokines, were significantly decreased at 12 weeks of sitagliptin treatment. In conclusion, treatment with sitagliptin increased the number of circulating CD34(+)CXCR4(+) cells by approximately 2-fold in patients with type 2 diabetes.
authors.affiliation: Department of Endocrinology and Metabolism, Dokkyo Medical University, 880 Kita-Kobayashi, Shimotsuga, Mibu, Tochigi, 321-0293, Japan. yaso@dokkyomed.ac.jp.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Aso
authors.affiliation: Department of Endocrinology and Metabolism, Dokkyo Medical University, 880 Kita-Kobayashi, Shimotsuga, Mibu, Tochigi, 321-0293, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Jojima
authors.affiliation: Department of Endocrinology and Metabolism, Dokkyo Medical University, 880 Kita-Kobayashi, Shimotsuga, Mibu, Tochigi, 321-0293, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iijima
authors.affiliation: Department of Endocrinology and Metabolism, Dokkyo Medical University, 880 Kita-Kobayashi, Shimotsuga, Mibu, Tochigi, 321-0293, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Internal Medicine, Koshigaya Hospital, Dokkyo Medical University, Koshigaya, Saitama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Terasawa
authors.affiliation: LSI Medience Corp., Itabashi-Ku, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fukushima
authors.affiliation: LSI Medience Corp., Itabashi-Ku, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Momobayashi
authors.affiliation: Department of Internal Medicine, Koshigaya Hospital, Dokkyo Medical University, Koshigaya, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hara
authors.affiliation: Department of Internal Medicine, Koshigaya Hospital, Dokkyo Medical University, Koshigaya, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takebayashi
authors.affiliation: Department of Medicine, Ishibashi General Hospital, Shimotsuke, Tochigi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kasai
authors.affiliation: Department of Internal Medicine, Koshigaya Hospital, Dokkyo Medical University, Koshigaya, Saitama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Inukai
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D066026:Endothelial Progenitor Cells; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000032:analysis; D000068900:Sitagliptin Phosphate / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018952:Antigens, CD34; C527276:CXCR4 protein, human; D054873:Dipeptidyl-Peptidase IV Inhibitors; D019718:Receptors, CXCR4; D000068900:Sitagliptin Phosphate
keywords: Chemokines; Endothelial progenitor cells; Sitagliptin