Increased GPIIB/IIIA expression and altered DNA-ploidy pattern in megakaryocytes of diabetic BB-rats
| Autor: | B. Schwippert, Diethelm Tschöpe, H. Rothe, P. Roesen, F. A. Gries, B. Schettler, U. Kiesel |
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| Rok vydání: | 1992 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Clinical Biochemistry Platelet Membrane Glycoproteins Biochemistry Megakaryocyte Downregulation and upregulation Internal medicine Diabetes mellitus medicine Animals Platelet Rats Inbred BB Thrombopoiesis Receptor Ploidies business.industry Platelet Count Tumor Necrosis Factor-alpha Insulin General Medicine DNA medicine.disease Flow Cytometry Hematopoiesis Rats Endocrinology Cytokine medicine.anatomical_structure Diabetes Mellitus Type 1 Regression Analysis Female business Megakaryocytes |
| Zdroj: | European journal of clinical investigation. 22(9) |
| ISSN: | 0014-2972 |
| Popis: | Hyperactive platelets contribute to angio-pathic 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 glyco-protein 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, triglycer-ides) 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-megakary-ocytes with upregulated GPIIB/IIIA expression and could reflect a mitogenic effect of insulin upon the endomitotic cycle of the megakaryocytes. |
| Databáze: | OpenAIRE |
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