title: Prostacyclin receptor expression on platelets of humans with type 2 diabetes is inversely correlated with hemoglobin A1c levels.
abstract: Inappropriate platelet aggregation can result in thrombosis and tissue ischemia. When compared to healthy human platelets, those of humans with type 2 diabetes (DM2) exhibit increased aggregation when stimulated. Activation of the platelet prostacyclin receptor (IPR) results in cAMP accumulation and inhibition of platelet aggregation. We hypothesized that DM2 platelets express decreased IPR when compared to platelets of healthy humans, resulting in decreased IPR agonist-induced cAMP accumulation. We measured IPR expression with radioligand binding of [(3)H]-iloprost, a stable prostacyclin analog, and with Western blotting of the IPR protein. Iloprost-stimulated platelet cAMP levels were used to identify the functional response to IPR activation. IPR binding, expression of the IPR protein and the levels of cAMP in platelets incubated with iloprost were significantly decreased in DM2 platelets when compared to platelets of healthy humans. IPR expression decreased in platelets as glycemic control of the subjects worsened, as indicated by increased hemoglobin A1c levels. Taken together, these findings suggest that reduced IPR expression in DM2 platelets may contribute to platelet hyperactivity in humans with type 2 diabetes.
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University, St. Louis, MO 63104, United States. Electronic address: stephmknebel@gmail.com.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Knebel
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University, St. Louis, MO 63104, United States. Electronic address: spraguer@slu.edu.
authors.forename: Randy S
authors.initials: RS
authors.lastname: Sprague
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University, St. Louis, MO 63104, United States. Electronic address: stephens@slu.edu.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Stephenson
mesh_terms: D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D008297:Male; D010974:Platelet Aggregation; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000096:biosynthesis*
chemical_list: D006442:Glycated Hemoglobin; D016285:Iloprost; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; C113936:PTGIR protein, human; C517652:hemoglobin A1c protein, human
keywords: Platelet; Prostacyclin receptor; Radioligand binding; Type 2 diabetes; Western blot; cAMP