Liraglutide preserves CD34⁺ stem cells from dysfunction Induced by high glucose exposure

Area of Science:

• Endocrinology
• Hematology
• Cardiovascular Medicine

Background:

• Type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular (CV) risk.
• Impaired function of CD34+ hematopoietic stem progenitor cells (HSPCs) contributes to this elevated CV risk in T2DM.
• Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are known to reduce mortality and CV events in T2DM patients.

Purpose of the Study:

• To investigate the expression of the GLP-1 receptor (GLP-1R) in CD34+ HSPCs.
• To determine if GLP-1RAs can improve the function of CD34+ HSPCs impaired by high glucose conditions.
• To explore the underlying molecular mechanisms of GLP-1RA action on CD34+ HSPCs.

Main Methods:

• CD34+ HSPCs were isolated from cord blood.
• GLP-1 receptor expression was assessed using RT-qPCR and Western Blot.
• Cells were exposed to high glucose (HG) and treated with liraglutide (LIRA), a GLP-1RA.
• Cell proliferation, CXCR4/SDF-1α axis activity, and reactive oxygen species (ROS) production were evaluated.
• Signaling pathways (cAMP, ERK1/2, AKT) were analyzed.

Main Results:

• CD34+ HSPCs express GLP-1R at both mRNA and protein levels.
• Liraglutide treatment prevented and rescued HG-induced impairment in HSPC proliferation, CXCR4/SDF-1α activity, and metabolic balance.
• Liraglutide stimulated intracellular cAMP, ERK1/2, and AKT signaling.
• A GLP-1R antagonist blocked these LIRA-dependent effects.

Conclusions:

• This study provides the first evidence that CD34+ HSPCs express the GLP-1 receptor.
• Liraglutide favorably impacts CD34+ HSPC dysfunction caused by high glucose exposure.
• These findings suggest a novel mechanism for the cardiovascular protective effects of GLP-1RAs in T2DM patients.