Streptozotocin-Induced Diabetes Mellitus – a Paradox of High Intrinsic Platelet Reactivity and Low In Vitro Platelet Aggregation

Scridon, Alina; Perian, Marcel; Mărginean, Alina; Vântu, A; Gherțescu, Doina; Fiscă, C; Halatiu, VB; Grigoras, T; Șerban, Răzvan Constantin

doi:10.4183/aeb.2019.46

Cited by 2 publications

(2 citation statements)

References 32 publications

(33 reference statements)

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“…In our previous ex vivo platelet aggregation study in STZ-induced diabetic rats, no increased platelet aggregation capacity was measured in diabetic rats either [ 42 ]. Consistent with the present data, decreased in vitro ADP- and AA-induced platelet aggregation was found in the STZ-induced diabetic rats compared to the healthy animals [ 54 ]. Paradoxically, these effects paralleled the high intrinsic hyperactivity of the platelets and might be explained by the time-dependent production of platelet aggregation-inhibiting factors.…”

Section: Discussionsupporting

confidence: 92%

Effects of sub-chronic, in vivo administration of sigma-1 receptor ligands on platelet and aortic arachidonate cascade in streptozotocin-induced diabetic rats

et al. 2022

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Background Diabetes mellitus is a chronic metabolic disorder which induces endothelial dysfunction and platelet activation. Eicosanoids produced from arachidonic acid regulate cellular and vascular functions. Sigma-1 receptors (S1R) are expressed in platelets and endothelial cells and S1R expression is protective in diabetes. Objectives Our aim was to examine the influence of sub-chronic, in vivo administered S1R ligands PRE-084, (S)-L1 (a new compound) and NE-100 on the ex vivo arachidonic acid metabolism of platelets and aorta in streptozotocin-induced diabetic rats. Methods The serum level of the S1R ligands was detected by LC-MS/MS before the ex vivo analysis. Sigma-1 receptor and cyclooxygenase gene expression in platelets were determined by RT-qPCR. The eicosanoid synthesis was examined with a radiolabelled arachidonic acid substrate and ELISA. Results One month after the onset of STZ-induced diabetes, in vehicle-treated, diabetic rat platelet TxB2 and aortic 6-k-PGF1α production dropped. Sub-chronic in vivo treatment of STZ-induced diabetes in rats for one week with PRE-084 enhanced vasoconstrictor and platelet aggregator and reduced vasodilator and anti-aggregator cyclooxygenase product formation. (S)-L1 reduced the synthesis of vasodilator and anti-aggregator cyclooxygenase metabolites and promoted the recovery of physiological platelet function in diabetic rats. The S1R antagonist NE-100 produced no significant changes in platelet arachidonic acid metabolism. (S)-L1 decreased the synthesis of vasoconstrictor and platelet aggregator cyclooxygenase metabolites, whereas NE-100 increased the quantity of aortic vasodilator and anti-aggregator cyclooxygenase products and promoted the recovery of diabetic endothelial dysfunction in the aorta. The novel S1R ligand, (S)-L1 had similar effects on eicosanoid synthesis in platelets as the agonist PRE-084 and in aortas as the antagonist NE-100. Conclusions S1R ligands regulate cellular functions and local blood circulation by influencing arachidonic acid metabolism. In diabetes mellitus, the cell-specific effects of S1R ligands have a compensatory role and aid in restoring physiological balance between the platelet and vessel.

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Section: Discussionsupporting

confidence: 92%

Effects of sub-chronic, in vivo administration of sigma-1 receptor ligands on platelet and aortic arachidonate cascade in streptozotocin-induced diabetic rats

et al. 2022

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“…However, none of the models previously described includes the use of insulin to correct or minimize the negative effects of hyperglycaemia. This circumstance has been acknowledged as a limitation to the study by several authors, in which potential biomarkers of platelet activation were analysed as instruments for the evaluation of thromboembolic risk in a model of long-term DM (28 weeks) induced by STZ (single dose of 60 mg/dL) [ 85 ].…”

Section: Similarity Of the Histological Finding In The Experimental A...mentioning

confidence: 99%

Experimental Models to Study Diabetes Mellitus and Its Complications: Limitations and New Opportunities

Martín-Carro

Donate‐Correa

Fernández-Villabrille

et al. 2023

IJMS

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Preclinical biomedical models are a fundamental tool to improve the knowledge and management of diseases, particularly in diabetes mellitus (DM) since, currently, the pathophysiological and molecular mechanisms involved in its development are not fully clarified, and there is no treatment to cure DM. This review will focus on the features, advantages and limitations of some of the most used DM models in rats, such as the spontaneous models: Bio-Breeding Diabetes-Prone (BB-DP) and LEW.1AR1-iddm, as representative models of type 1 DM (DM-1); the Zucker diabetic fatty (ZDF) and Goto-kakizaki (GK) rats, as representative models of type 2 DM (DM-2); and other models induced by surgical, dietary and pharmacological—alloxan and streptozotocin—procedures. Given the variety of DM models in rats, as well as the non-uniformity in the protocols and the absence of all the manifestation of the long-term multifactorial complications of DM in humans, the researchers must choose the one that best suits the final objectives of the study. These circumstances, added to the fact that most of the experimental research in the literature is focused on the study of the early phase of DM, makes it necessary to develop long-term studies closer to DM in humans. In this review, a recently published rat DM model induced by streptozotocin injection with chronic exogenous administration of insulin to reduce hyperglycaemia has also been included in an attempt to mimic the chronic phase of DM in humans.

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Streptozotocin-Induced Diabetes Mellitus – a Paradox of High Intrinsic Platelet Reactivity and Low In Vitro Platelet Aggregation

Cited by 2 publications

References 32 publications

Effects of sub-chronic, in vivo administration of sigma-1 receptor ligands on platelet and aortic arachidonate cascade in streptozotocin-induced diabetic rats

Effects of sub-chronic, in vivo administration of sigma-1 receptor ligands on platelet and aortic arachidonate cascade in streptozotocin-induced diabetic rats

Experimental Models to Study Diabetes Mellitus and Its Complications: Limitations and New Opportunities

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