Sitagliptin, a dipeptidyl peptidase-4 inhibitor, increases the number of circulating CD34 + CXCR4 + cells in patients wi
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ORIGINAL ARTICLE
Sitagliptin, a dipeptidyl peptidase-4 inhibitor, increases the number of circulating CD34+CXCR4+ cells in patients with type 2 diabetes Yoshimasa Aso1 • T. Jojima1 • T. Iijima1 • K. Suzuki1 • T. Terasawa2 M. Fukushima3 • A. Momobayashi3 • K. Hara2 • K. Takebayashi2 • K. Kasai4 • T. Inukai2
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Received: 27 January 2015 / Accepted: 11 July 2015 Ó Springer Science+Business Media New York 2015
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 cellderived factor (SDF)-1a, 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)/106 cells at baseline to 55.5 (31.5, 80.5)/106 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-1a 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 & Yoshimasa Aso [email protected] 1
Department of Endocrinology and Metabolism, Dokkyo Medical University, 880 Kita-Kobayashi, Shimotsuga, Mibu, Tochigi 321-0293, Japan
2
Department of Internal Medicine, Koshigaya Hospital, Dokkyo Medical University, Koshigaya, Saitama, Japan
3
LSI Medience Corp., Itabashi-Ku, Tokyo, Japan
4
Department of Medicine, Ishibashi General Hospital, Shimotsuke, Tochigi, Japan
number of circulating CD34?CXCR4? cells by approximately 2-fold in patients with type 2 diabetes. Keywords Endothelial progenitor cells Sitagliptin Chemokines
Introduction Circulating endothelial progenitor cells (EPCs) are involved in repairing vascular endothelial damage and initiating neovascularization in vivo [1]. EPCs can be mobilized from the bone marrow to the peripheral circulation in response to tissue ischemia [2]. Several studies reported the decreased number of circulating EPCs with their impaired function in patients with type 2 diabetes [3, 4]. Because reduced levels of circulating EPCs are associated with endothelial dysfunction and development of cardiovascular disease (CVD) in patients with type 2 diabetes, raising the number of circulating EPCs may be a therapeutic strategy to prevent CVD for these patients. Stromal cell-derived factor (SDF)-1a, which is also known as CXCL12, is a chemokine that plays a critical
