Effects of Incretins on Human Platelet Function
Condition: Inhibition of Platelet Aggregation by Incretins
Study type: Observational

Summary: 
      Novel drugs for the treatment of patients with diabetes are of interest for cardiologists if
      they reduce the risk of cardiovascular events. However, as documented by the current
      discussion about the potential benefits of glitazones, high hopes can fail. Initial
      beneficial cardiovascular effects shown in proof-of-concept studies were muted by the
      apparent higher mortality in the metaanalysis of studies with rosiglitazone. The rapidly
      increasing use of GLP-1 analogues and DPP-4 (Dipeptidyl protease 4) inhibitors for the
      treatment of type 2 diabetes mellitus may be of major interest for the cardiologist.
      Potential beneficial actions on the cardiovascular system so far shown in animal experiments
      and small proof of concept studies may provide the rationale for using these drugs
      specifically in diabetic patients with secondary complications such as macrovascular disease
      or diabetic cardiomyopathy. Theoretically, these new therapies could also proof beneficial in
      patients with heart failure, independently of concomitant diabetes mellitus. However, many
      unanswered questions need to be addressed in the near future to extend the experimental
      findings to potential benefits of real life patients. In summary a new class of antidiabetic
      drugs, which could possibly directly influence cardiovascular effects of diabetes mellitus
      and thus possibly treat or even prevent life threatening complications has become available.

      Then our working hypothesis was that incretins may have desirable cardiovascular outcomes
      through modulating platelet function. In order to test this hypothesis we propose to assess
      the presence of their specific receptors in isolated human platelets. In addition, we
      proposed to sudy the effect of the endogenous incretins (glucagon-like peptide 1 and gastric
      inhibitory peptide) on human platelet function isolated in a test tube.
    

Detailed description: 
      Aims and Methods: The prevalence of Type 2 diabetes (T2D) continues to increase globally and
      brings with it a parallel increase in the associated cardiovascular disease complications.
      Correction of platelet hyperactivity holds promise for this high-risk population of T2D
      patients by contributing to restore normal hemostasis, which has lead to the search for new
      antiagregant drugs. Then, our aim was to study whether incretins may modulate platelet
      function; for this purpose platelets from healthy subjects who were not taken any medication
      were studied. Besides, normal mature megakaryocytes obtained by culture of human cord blood
      derived-CD34+ hematopoietic progenitor cells were also studied.

      For platelet function studies, platelet aggregation was tested in the absence and presence of
      different concentrations (10-9 M to 10-5 M) of glucagon-like peptide-1,GLP1-(7-36)NH2, and
      glucose-dependent insulinotropic polypeptide (GIP) agonist by a turbidimetricassay. The
      effect of 300 mg/dLglucose added to the media was also evaluated. GLP1R (glucagon-like
      peptide 1 receptor) and GIPR (GIP receptor) mRNA expression was evaluated by Real Time PCR in
      platelet and megakaryocyte total mRNA. The putative presence of their proteins was assayed by
      western blot and flow cytometry in both samples.
    

Intervention name(s): venous puncture
Intervention type(s): Other
Intervention description(s): Blood for in vitro studies will be drawn
Other intervention name(s): volunteers
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Healthy subjects
      
Keywords: GLP1; GIP; platelets; human; aggregation