Background: Type 2 diabetes (T2D) is associated with reduced numbers and impaired function of circulating angiogenic cells (CAC) which contributes to the progression of atherosclerosis and microvascular disease. Previous studies suggest that short-term infusion of unacylated ghrelin (UAG) normalizes CAC number in patients with T2D. To determine dose-dependent effects of short-term infusion of UAG in T2D patients using a cross-over model, and of long-term infusion of UAG in obese mice, on differentiation of monocyte progenitors into CAC.
Methods: Eight overweight T2D patients were infused overnight with 3 and 10 µg/kg/h of UAG in a double-blind, placebo-controlled cross-over study. To assess the effects of long-term UAG treatment, obese mice were infused with UAG for 4 weeks. Monocyte progenitors were assessed for their ability to differentiate into CAC in vitro.
Results: In T2D patients, UAG treatment caused a reduction in differentiation of CAC, dependent on UAG dose and differentiation method. However, mice treated with UAG showed a significant increase in differentiation of bone marrow progenitors into CAC.
Conclusion: UAG causes a minor suppressive effect on CAC development after short-term treatment in humans, but experiments in mice suggest that long-term treatment has beneficial effects on CAC formation. The Netherlands Trial Register: TC=2487

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Keywords Circulating angiogenic cell, Diabetes, Insulin resistant, Obese, Unacylated ghrelin
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Journal Diabetology and Metabolic Syndrome
Özcan, B, Leenen, P.J.M, Delhanty, P.J.D, Baldeón Rojas, L, Neggers, S.J.C.M.M, & van der Lely, A-J. (2017). Unacylated ghrelin modulates circulating angiogenic cell number in insulin-resistant states. Diabetology and Metabolic Syndrome (Vol. 9). doi:10.1186/s13098-017-0239-8