Demonstration and partial characterization of insulin receptors in human platelets.

Abstract

A B S T R A C T Recently, evidence has been reported to suggest that human platelets like several other circulating blood cells may bind insulin. To examine whether human platelets contain specific insulin receptors, washed human platelets suspended in Hepes buffer were incubated at 24°C with 1251-insulin in the presence and absence of unlabeled insulin and specific insulin binding was determined. Insulin binding by platelets increased progressively with time of incubation to reach a maximum at 3 h and was proportional to the number of platelets in the incubation mixture. Maximum insulin binding was observed at pH 8. Insulin degradation by platelets as assessed by TCA precipitability and reincubation studies was minimal. Scatchard analysis ofthe binding data and dissociation studies revealed evidence of negative cooperativity of the platelet insulin receptor. A high affinity dissociation constant of _3 x 109 M-1 was determined and the concentration of platelet insulin receptors was estimated as 25 binding sites/,un2 platelet surface area. Binding of 1251-insulin by platelets was inhibited by unlabeled porcine insulin and to a lesser extent by catfish insulin and porcine proinsulin but not by glucagon, prolactin, growth hormone, and thrombin. The findings indicate that human platelets contain specific insulin receptors. The significance of the platelet insulin receptor, particularly with respect to altered platelet function in diabetes mellitus, remains to be determined.

The effects of treatment with Liraglutide on atherothrombotic risk in obese young women with polycystic ovary syndrome and controls

“…The improvement in platelet function with weight loss was related to a reduction in abdominal obesity and associated reduction in IR, inflammation and oxidative stress levels [9,27]. Platelets have been found to express the insulin receptor [36] and while insulin is believed to reduce platelet sensitivity to aggregating agents, its function in IR states for example type 2 diabetes and obesity is thought to be impaired [37]. As PCOS, similar to type 2 diabetes, is associated with increased IR independent of obesity, it is possible that platelets from women with PCOS are more resistant to the inhibitory effects of liraglutide, and/or associated weight loss, perhaps suggesting an inherent defect in platelet function in PCOS.…”

Platelet Inhibition by Insulin Is Absent in Type 2 Diabetes Mellitus

“…25 After receptor activation, IRS-1 is recruited and tyrosine phosphorylated leading to activation of pathways involving PKB and p38 mitogen-activated protein kinases in addition to inhibition of G i ␣ 2 9,18,26 . Possibilities for abnormal insulin signaling in DM2 platelets are defects in the insulin receptor ␤-subunit, IRS-1, and the tyrosine phosphorylation of G i ␣ 2 together with the different tyrosine kinases and phosphatases that control these processes.…”

Type 2 Diabetes: An Atherothrombotic Syndrome

“…phenotype in the vasculature that prevents the formation of thrombi within healthy segments of blood vessels [168]. Platelet function is also regulated by insulin acting via cell surface receptors [169]. Insulin has been shown in both invivo and in-vitro studies to antagonise the platelet activating/aggregating effects of a number of agonists, including ADP, PAF and collagen [170].…”