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Unacylated ghrelin modulates circulating angiogenic cell number in insulin-resistant states
Behiye Özcan1, Pieter J M Leenen2, Patric J D Delhanty1
1Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
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.
Insights
Short-term unacylated ghrelin (UAG) infusion in type 2 diabetes patients reduced circulating angiogenic cells (CAC) development. However, long-term UAG treatment in mice increased CAC formation, suggesting potential therapeutic benefits.
Area of Science:
- Endocrinology
- Vascular Biology
- Metabolic Diseases
Background:
- Type 2 diabetes (T2D) is linked to diminished circulating angiogenic cells (CAC), exacerbating atherosclerosis and microvascular complications.
- Previous research indicated short-term unacylated ghrelin (UAG) infusion may normalize CAC counts in T2D patients.
Purpose of the Study:
- To investigate the dose-dependent effects of short-term UAG infusion on CAC differentiation in T2D patients.
- To evaluate the impact of long-term UAG infusion on monocyte progenitor differentiation into CAC in obese mice.
Main Methods:
- A double-blind, placebo-controlled crossover study involving eight T2D patients receiving overnight UAG infusions (3 and 10 µg/kg/h).
- Obese mice underwent 4-week UAG infusions to assess long-term effects.
- In vitro assessment of monocyte progenitor differentiation into CAC.
Main Results:
- In T2D patients, UAG administration resulted in a dose-dependent reduction in CAC differentiation.
- Conversely, obese mice treated with UAG exhibited a significant enhancement in bone marrow progenitor differentiation into CAC.
Conclusions:
- Short-term UAG treatment in humans shows a modest suppressive effect on CAC development.
- Long-term UAG administration in mice suggests a beneficial role in promoting CAC formation.
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