Red Cell Deformability, Platelet Aggregation, and Insulin Action

Vague, P; Juhan, I

doi:10.2337/diab.32.2.s88

Cited by 45 publications

(22 citation statements)

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“…Previously suggested mechanisms include hypoinsulinemia (23), increased internal viscosity (24), increased erythrocyte sorbitol concentration (25), and increased erythrocyte membrane rigidity cause by glycation of erythrocyte membranes (26). Still other investigators have failed to detect any alteration in RBC-df in diabetic patients (27,28).…”

Section: Discussionmentioning

confidence: 99%

Correction of Erythrocyte Deformability Defect in ALX-Induced Diabetic Rabbits After Treatment With Aminoguanidine

Brown

Zhao²,

Álvaro³

et al. 1993

Diabetes

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To test whether treatment with aminoguanidine, a drug known to prevent cross-linking between glycated proteins, is effective in improving reduced erythrocyte deformability in diabetes, we studied a group (n = 6) of ALX-induced long-term (12.7 +/- 2.2 mo of hyperglycemia) diabetic New Zealand white rabbits before and after 20 wk of treatment with aminoguanidine (100 mg.kg-1 x day-1). The key findings were as follows: 1) at 12 wk of treatment with aminoguanidine, mean erythrocyte deformability normalized and remained within the normal reference range throughout the period of aminoguanidine administration; 2) 10 wk after discontinuing aminoguanidine in a subset of diabetic rabbits, mean erythrocyte deformability deteriorated by approximately 50%; 3) blood glucose and total GHb did not vary significantly during treatment with aminoguanidine nor after its discontinuation.

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Section: Discussionmentioning

confidence: 99%

Correction of Erythrocyte Deformability Defect in ALX-Induced Diabetic Rabbits After Treatment With Aminoguanidine

Brown

Zhao²,

Álvaro³

et al. 1993

Diabetes

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“…Thus, we anticipate that the study will impact broadly on the research of red cells, cellular mechanosensing, and clinical studies related to red cell disorders and vascular disease. (1)(2)(3)(4). Recent studies show that, in response to shear-induced stretch, RBCs release adenosine triphosphate (ATP) (5)(6)(7)(8)(9), suggesting the existence of mechanotransductive pathways in RBCs.…”

mentioning

confidence: 99%

Piezo1 regulates mechanotransductive release of ATP from human RBCs

Çinar

Zhou

DeCourcey

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

166

157

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Piezo proteins (Piezo1 and Piezo2) are recently identified mechanically activated cation channels in eukaryotic cells and associated with physiological responses to touch, pressure, and stretch. In particular, human RBCs express Piezo1 on their membranes, and mutations of Piezo1 have been linked to hereditary xerocytosis. To date, however, physiological functions of Piezo1 on normal RBCs remain poorly understood. Here, we show that Piezo1 regulates mechanotransductive release of ATP from human RBCs by controlling the shear-induced calcium (Ca 2+ ) influx. We find that, in human RBCs treated with Piezo1 inhibitors or having mutant Piezo1 channels, the amounts of shear-induced ATP release and Ca 2+ influx decrease significantly. Remarkably, a critical extracellular Ca 2+ concentration is required to trigger significant ATP release, but membrane-associated ATP pools in RBCs also contribute to the release of ATP. Our results show how Piezo1 channels are likely to function in normal RBCs and suggest a previously unidentified mechanotransductive pathway in ATP release. Thus, we anticipate that the study will impact broadly on the research of red cells, cellular mechanosensing, and clinical studies related to red cell disorders and vascular disease. Previous studies have shown that the addition of chemicals that stiffen RBC membranes decreases the amount of ATP released (9, 16), indicating that deformation of the cell membrane is a necessary trigger. In addition, biological mediators, such as cystic fibrosis transmembrane conductance regulator (CFTR) and pannexin-1 hemichannels, are involved in the release pathways of mechanotransductive ATP release from RBCs (9,14,17,18). Inhibition of CFTR leads to an impaired ATP release from deformed RBCs (14). Recent studies, including our previous findings, suggest that interactions between membrane-associated actin and CFTR play important roles in the mechanotransductive ATP release from RBCs (9, 17). Pannexin-1, however, is a channel-forming protein and has been suggested as a mechanosensing ATP release channel (18). Under osmotic stress, for example, ATP released from RBCs was attenuated by carbenoxolone, a highly effective pannexin channel blocker, suggesting that pannexin-1 might be one of the conductance channels responsible for the mechanotransductive release of ATP (18). Although progress has been made in understanding mechanotransductive ATP release from RBCs, many questions remain about the signal transduction pathways. For example, how does mechanical force transduce signals to ATP release channels? Are there any stretch-activated ion channels on RBCs that may sense mechanical forces and activate ATP release? If so, are there any secondary messengers that could be generated by mechanical stimuli and regulate ATP release?Piezo proteins (Piezo1 and Pizeo2) are recently identified mechanically activated cation channels in mammals (19,20) and can be fully activated without involvement of additional proteins (20, 21). Piezo-induced cationic currents were first observe...

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“…The results of this study indicate that IDA leads to significant hemorheological changes in children, such as decrement in RBC deformability, aggregation, and plasma and whole blood viscosity at standard Hct and that the decrements in these parameters return to control levels following iron treatment. Hemorheological parameters were reported to be influenced by the presence of hyperlipidemia, hyperglycemia, and hypercholesterolemia [11][12][13]. To minimize the presence of these conditions, blood samples were obtained in the morning before breakfast and lipid, glucose, and cholesterol levels of the children were all found to be at normal levels.…”

Section: Discussionmentioning

confidence: 99%