Studies on calcium exchange in platelets in human diabetes

Abstract. Calcium has a key role in platelet aggregation. In order to assess the role of calcium metabolism in the platelet in diabetes mellitus, calcium exchange into and out of the cytosol was investigated in platelets from eight patients with insulin-treated diabetes with a mean duration of 10 years without any clinical complications. Their mean HbA_Ic (glycosylated haemoglobin) was 9% (normal range 3·4–5·4%). Influx rate of ⁴⁵Ca²⁺ was significantly increased by 35% in diabetic platelets compared with controls. The efflux rate was significantly reduced during the first 15 min but total efflux measured over 2 h was equal in diabetic and control platelets. Access to sequestered non-mitochondrial calcium in the dense tubular system was gained by permeabilization of the cells with saponin. Into cells loaded with ⁴⁵Ca²⁺, Inositol 1, 4, 5 triphosphate (IP₃) was introduced and release of the sequestered ion would be determined. In control platelets calcium release was prompt and amounted to 43%. In diabetic platelets the response to IP₃ was blunted and was only 17%. The nutritional and hormonal status influenced the response to IP₃ in diabetes and, to a lesser extent, in controls. In the fasting state and without insulin the release was reduced but in the fed state and after insulin the release of calcium from diabetic platelets was equal to those of controls. It is concluded that abnormalities exist in platelet calcium handling in diabetes that can be influenced by insulin and the nutritional status. These abnormalities may well contribute to the increased ability for platelet aggregation in the diabetic state, and the insulin and nutritional influence underlines the importance of the metabolic status when studying platelet function.