Effects of Insulin on Calcium Metabolism and Platelet Aggregation

Abstract

The influence of insulin on platelets in vitro has not been exhaustively investigated. To clarify whether insulin affects Ca2+ metabolism in platelets directly or through alteration of other systems regulating intracellular Ca2+ homeostasis, we examined the effect of insulin both alone and in combination with prostaglandin E1 on platelet aggregation and Ca2+ metabolism. Incubation of rat platelets with insulin reduced thrombin-induced Ca2+ influx but did not change thrombin-evoked release of Ca2+ from internal stores or the size of internal Ca2+ stores. The interactive effects of insulin with prostaglandin E1 were only additive, and insulin did not augment the effects of prostaglandin E1 on platelet Ca2+ metabolism. In contrast, insulin did not inhibit thrombin-induced platelet aggregation but did augment inhibition of platelet aggregation by prostaglandin E1. Our results suggest that insulin inhibits platelet function by both prostaglandin E1-dependent and -independent mechanisms.

Diabetes and Antiplatelet Therapy in Acute Coronary Syndrome

“…39 Among IRS-dependent factors, insulin resistance provokes an increase in intracellular calcium concentration, leading to enhanced platelet degranulation and aggregation. 40 However, the precise mechanism by which calcium concentration is increased is not yet fully elucidated. 41,42 IRSindependent pathways are also involved in platelet hyperreactivity caused by insulin resistance such as impairment in platelet sensitivity to nitric oxide (NO) and prostacyclin.…”

“…39 Az IRS-függő tényezők közül az inzulinrezisztencia az intracelluláris kalciumkoncentráció növekedését idé-zi elő, ami a vérlemezkék fokozott degranulációjához és aggregációjához vezet. 40 A kalciumkoncentráció növekedésének pontos mechanizmusa azonban még nem teljesen ismert. 41,42 Az IRS-től független folyamatok is hozzájárulnak az inzulinrezisztencia által kiváltott thrombocyta-hiperreaktivitáshoz, úgy mint a vérlemezkék nitrogén-monoxid (NO) és a prosztaciklin iránti csökkent érzékenysége.…”

Antiplatelet Therapy in Patients With Diabetes Mellitus and Acute Coronary Syndrome

“…9 Moreover, insulin resistance and/or deficiency in diabetic patients have been associated with impairment in the response to antithrombotic molecules (such as prostacyclin) 10 and contribute to platelet dysfunction by insulin receptor substrate-dependent effects, causing a rise in the intracellular calcium concentration and subsequent enhanced platelet degranulation. 11 Upregulation of glycoprotein (GP) IIb/IIIa surface receptors, 12 amplification of P2Y12 signaling, 13 and overproduction of reactive oxygen species 14 also contribute to the platelet dysfunction of diabetic patients; finally, metabolic conditions frequently associated with DM (ie, obesity, dyslipidemia and systemic inflammation) may also play a role. 7 Despite the use of long-term dual antiplatelet therapy after 34 PATTI G et al…”

Effect of Insulin and Angiotensin II on Cell Calcium in Human Skin Fibroblasts

“…4 In vitro, acute insulin exposure attenuates intracellular calcium (Ca i 2ϩ ) mobilization and contractile response to pressure agents in rat aorta, 5 in cultured vascular smooth muscle cells, 6 and in platelets. 7 This may result from an action on Ca 2ϩ -ATPase, voltage-and receptor-operated Ca 2ϩ -channels, vasoconstrictor receptors, G protein, phospholipase C, or inositoltrisphosphate (IP 3 )-sensitive Ca i 2ϩ release channels, 8 but its precise mechanism remains to be defined.…”