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Selected Publication:
Schaeffer, G; Wascher, TC; Kostner, GM; Graier, WF.
Alterations in platelet Ca2+ signalling in diabetic patients is due to increased formation of superoxide anions and reduced nitric oxide production.
Diabetologia. 1999; 42(2):167-176
Doi: 10.1007%2Fs001250051135
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- Leading authors Med Uni Graz
- Graier Wolfgang
- Co-authors Med Uni Graz
- Kostner Gerhard
- Wascher Thomas
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- Abstract:
- Increased aggregation of platelets might contribute to the development of vascular complication in diabetes mellitus. In this study release of superoxide anions, intracellular Ca2+ signalling and nitric oxide formation stimulated by the receptor-dependent agonist adenosine 5 '-diphosphate (ADP) and the receptor-independent stimulus thapsigargin, were compared in platelets isolated from patients with Type II (non-insulin-dependent) diabetes mellitus and healthy control subjects. Diabetes augmented intracellular Ca2+ release and Ca2+ entry to ADP by 40 and 44% (control subjects: n = 11; diabetic: n = 6), while the median effective concentration (EC50) of ADP to initiate Ca2+ signalling was similar in both groups. The effect of thapsigargin on Ca2+ concentration was increased by 69% in diabetic patients (control subjects: n = 22; diabetic patients: n = 9). In addition, release of superoxide anions was 70% greater in diabetic patients (control subjects: n = 9; diabetic patients: n = 6). Treatment of platelets from control subjects with the superoxide anion-generating mixture xanthine oxidase and hypoxanthine or buthioninesulphoximine (BSO) mimicked the effect of diabetes on platelet Ca2+ signalling. The antioxidant glutathione normalized enhanced Ca2+ response in the diabetic group (control subjects: n = 5: diabetic patients: n = 6). Basal and thapsigargin-evoked nitric oxide synthase activity was reduced in the diabetic group by 85 and 64%, respectively (control subjects: n = 13; diabetic subjects: n = 13). The nitric oxide-donor 2-(N,N-diethylamino)-diazenolate-2-oxide sodium (DEA/NO) normalized enhanced Ca2+ signalling in platelets preincubated with xanthine oxidase and hypoxanthine (n = 12) and in those from diabetics (control subjects: n = 6; diabetic patients: n = 6). Inhibition of nitric oxide synthase by N-nitro-L-arginine (L-NA) augmented thapsigargin-induced Ca2+ signalling by 51% (n = 8). These data indicate that in diabetes platelet Ca2+ signalling might be enhanced by excessive superoxide production and an attenuated negative direct or indirect feedback control by nitric oxide, due to its reduced production.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenosine Diphosphate - pharmacology
- Adult - pharmacology
- Antioxidants - pharmacology
- Blood Platelets - cytology
- Calcium - blood
- Calcium Signaling - blood
- Diabetes Mellitus, Type 2 - blood
- Enzyme Inhibitors - pharmacology
- Female - pharmacology
- Glutathione - pharmacology
- Humans - pharmacology
- Male - pharmacology
- Middle Aged - pharmacology
- Nitric Oxide - blood
- Nitric Oxide Synthase - antagonists and inhibitors
- Nitroarginine - pharmacology
- Platelet Aggregation - pharmacology
- Superoxides - blood
- Thapsigargin - pharmacology
- Find related publications in this database (Keywords)
- Platelet
- Ca2+ Signaling
- Nitric Oxide
- Superoxide Anions
- ADP
- Thapsigargin