title: Increased GPIIB/IIIA expression and altered DNA-ploidy pattern in megakaryocytes of diabetic BB-rats.
abstract: Hyperactive platelets contribute to angiopathic complications in diabetes mellitus. It is unclear whether the increased platelet function is a primary pathogenetic factor in diabetes or follows vascular injury. Increased platelet size and numbers of glycoprotein receptors on diabetic platelets suggest that thrombopoiesis is altered in diabetes mellitus. For further support of this hypothesis we studied whether megakaryocytes are changed with regard to the DNA-ploidy pattern and the GPIIB/IIIA expression in 10 acute diabetic (AD) and 24 insulin treated diabetic (ITD) BB rats in comparison with 22 diabetes resistant (ND) BB rats. In the AD group megakaryocyte size (P = 0.035) and the modal DNA-ploidy distribution dropped (P = 0.0001) concomitant with increased TNF-alpha activity (P = 0.001). GPIIB/IIIA expression and the peripheral platelet status were unchanged. After 4 weeks of insulin substitution metabolic parameters (glucose, cholesterol, triglycerides) were lowered, but remained still elevated. As compared to the AD group the modal DNA-ploidy pattern reversed, but the relative percentage of 64n megakaryocytes increased 2.3-fold and GPIIB/IIIA expression increased 1.6-fold. Simultaneously, the peripheral platelet count and size increased. From these results we conclude that alterations of the megakaryocyte compartment occur at early onset of diabetes. These changes could reflect a response to increased systemic cytokine production during inflammatory islet cell destruction. The peripheral platelet thrombotic potency increased with insulin treatment. This was associated with an increase of 64n-megakaryocytes with upregulated GPIIB/IIIA expression and could reflect a mitogenic effect of insulin upon the endomitotic cycle of the megakaryocytes.
authors.affiliation: Cellular Haemostasis Group, Diabetes Research Institute, Heinrich Heine University of Düsseldorf, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Tschöpe
authors.forename: B
authors.initials: B
authors.lastname: Schwippert
authors.forename: B
authors.initials: B
authors.lastname: Schettler
authors.forename: U
authors.initials: U
authors.lastname: Kiesel
authors.forename: H
authors.initials: H
authors.lastname: Rothe
authors.forename: P
authors.initials: P
authors.lastname: Roesen
authors.forename: F A
authors.initials: FA
authors.lastname: Gries
mesh_terms: D000818:Animals; D004247:DNA / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006410:Hematopoiesis; D008297:Male; D008533:Megakaryocytes / Q000473:pathology*; D010976:Platelet Count; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D011003:Ploidies; D051381:Rats; D011913:Rats, Inbred BB; D012044:Regression Analysis; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D010980:Platelet Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D004247:DNA