Maternal Insulin Therapy Increases Fetal Endothelial Progenitor Cells During Diabetic Pregnancy

Fadini, Gian Paolo; Baesso, Ilenia; Agostini, Carlo; Cuccato, Emily; Nardelli, Giovanni Battista; Lapolla, Annunziata; Avogaro, Angelo

doi:10.2337/dc07-1996

Cited by 11 publications

(7 citation statements)

References 14 publications

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“…Nguyen et al have shown that myofibroblast progenitor cells are increased in number in diabetic patients compared with controls [21], highlighting that such a dysfunction is selective for cardio-and vasculoprotective progenitors, while there may be a concomitant expansion of circulating cells with pro-remodelling activities. If a bone marrow defect is present, it seems to be reversible, because glucose-lowering therapies has been shown to restore the level of circulating progenitors to some extent [22][23][24]. Finally, as shown previously and confirmed by Egan et al, progenitor cell decline was linearly correlated with the severity of diabetic complications.…”

supporting

confidence: 64%

An underlying principle for the study of circulating progenitor cells in diabetes and its complications

Fadini

2008

Diabetologia

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supporting

confidence: 64%

An underlying principle for the study of circulating progenitor cells in diabetes and its complications

Fadini

2008

Diabetologia

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“…There is evidence that improved metabolic control in patients with diabetes improves EPC number and function (41–43) in adults. In one study (42), insulin treatment for 4 weeks increased EPCs by 65.6 ± 62.7% ( P = 0.007).…”

Section: Discussionmentioning

confidence: 99%

Endothelial Progenitor Cells Are Related to Glycemic Control in Children With Type 1 Diabetes Over Time

et al. 2013

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OBJECTIVEThe risk of cardiovascular death before the age of 40 is 20-fold higher in patients with type 1 diabetes mellitus (T1DM). Endothelial progenitor cells (EPCs) predict cardiovascular morbidity and mortality in patients without diabetes. We hypothesized that EPCs are modified in children with T1DM and are related to characteristics of T1DM such as glycemic control.RESEARCH DESIGN AND METHODSChildren (n = 190; 156 T1DM subjects and 34 control subjects) were included in an observational cohort study and matched for age and sex. EPCs were enumerated by flow cytometry at the beginning (cross-sectional) and 1 year later (longitudinal). To analyze changes of variables during the observation, Δ values were calculated.RESULTSEPCs were significantly reduced in T1DM children versus control subjects (609 ± 359 vs. 1,165 ± 484, P < 0.001). Multivariate regression modeling revealed that glycated hemoglobin A1c (HbA1c) was the strongest independent predictor of EPCs (β = −0.355, P < 0.001). Overall glycemic control at the beginning and end of study did not differ (7.8 ± 1.2 vs. 7.8 ± 1.2 relative %, P = NS), but we observed individual HbA1c changes of −4.30/+3.10 relative %. The strongest EPC increase was observed in the patients with the most favorable HbA1c lowering during the 1-year follow-up. Accordingly, the strongest EPC decrease was demonstrated in the patients with the strongest HbA1c worsening during the time period.CONCLUSIONSThis is the first prospective study demonstrating diminished EPCs in children with T1DM. The association of better glycemic control with an increase in EPC numbers within 1 year suggests that a reduction of the high cardiovascular disease burden might be mediated likewise.

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“…It can therefore be speculated that insulin therapy in humans could improve vascular function via stimulation of EPC mobilization, differentiation, and vascular regeneration. Increased mobilization of fetal endothelial progenitor cells by insulin therapy was recently shown in diabetic pregnancy (48). However, in view of the receptor affinities for human insulin, this might only be the case in patients treated with high daily doses of human insulin or glargine, which has a 6-fold increased affinity for the IGF-1 receptor (22).…”

Section: N S U L I N E F F E C T S O N E N D O T H E L I a L P R O mentioning

confidence: 93%

Insulin Stimulates the Clonogenic Potential of Angiogenic Endothelial Progenitor Cells by IGF-1 Receptor-Dependent Signaling

Humpert

Djuric

Zeuge

et al. 2008

Mol Med

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Endothelial progenitor cells (EPCs) have been shown to be involved in vascular regeneration and angiogenesis in experimental diabetes. Because insulin therapy mobilizes circulating progenitor cells, we studied the effects of insulin on outgrowth of EPCs from peripheral blood mononuclear cells of healthy volunteers and patients with type 2 diabetes. Insulin increased the formation of EPC colony-forming units in a dose-dependent manner, half-maximal at 1.5 nM and peaking at 15 nM. Inhibiting the insulin receptor with neutralizing antibodies or antisense oligonucleotides had no effect on EPC outgrowth.1 In contrast, targeting the human insulin-like growth factor 1 (IGF-1) receptor with neutralizing antibodies significantly suppressed insulin-induced outgrowth of EPCs from both healthy controls and patients with type 2 diabetes. This IGF-1 receptor-mediated insulin effect on EPC growth was at least in part dependent on MAP kinases 2 and was abrogated when extracellular signal-regulated kinase 1/2 (Erk1/2) and protein kinase 38 (p38) activity was inhibited. To study the functional relevance of the observed insulin effects, we studied EPCinduced tube formation of bovine endothelial cells in vitro. Insulin-stimulated EPCs incorporated into the endothelial tubes and markedly enhanced tube formation. In conclusion, this is the first study showing an insulin-mediated activation of the IGF-1 receptor leading to an increased clonogenic and angiogenic potential of EPCs in vitro.

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Maternal Insulin Therapy Increases Fetal Endothelial Progenitor Cells During Diabetic Pregnancy

Cited by 11 publications

References 14 publications

An underlying principle for the study of circulating progenitor cells in diabetes and its complications

An underlying principle for the study of circulating progenitor cells in diabetes and its complications

Endothelial Progenitor Cells Are Related to Glycemic Control in Children With Type 1 Diabetes Over Time

Insulin Stimulates the Clonogenic Potential of Angiogenic Endothelial Progenitor Cells by IGF-1 Receptor-Dependent Signaling

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