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High Dose of Metformin Decreases Susceptibility to Occlusive Arterial Thrombosis in Diabetic Mice
INTRODUCTION: Metformin is the most prescribed medication in Diabetes Mellitus(DM). Metformin has shown to decrease mean platelet volume, with promising antiplatelet effects. High doses of Metformin have also been associated with hypercoagulation. We hypothesize that Metformin will protect DM mice f...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10653203/ https://www.ncbi.nlm.nih.gov/pubmed/37975061 |
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author | Alvidrez, Roberto I. Mota Annarapu, Gowtham K. Srinivasan, Amudan J. Liu, Zeyu Yazdani, Hamza O. Nolfi-Donegan, Deidre Simmons, Richard L. Shiva, Sruti Neal, Matthew D. |
author_facet | Alvidrez, Roberto I. Mota Annarapu, Gowtham K. Srinivasan, Amudan J. Liu, Zeyu Yazdani, Hamza O. Nolfi-Donegan, Deidre Simmons, Richard L. Shiva, Sruti Neal, Matthew D. |
author_sort | Alvidrez, Roberto I. Mota |
collection | PubMed |
description | INTRODUCTION: Metformin is the most prescribed medication in Diabetes Mellitus(DM). Metformin has shown to decrease mean platelet volume, with promising antiplatelet effects. High doses of Metformin have also been associated with hypercoagulation. We hypothesize that Metformin will protect DM mice from occlusive arterial thrombus formation by altering platelet activation and mitochondrial bioenergetics. METHODS: DM was developed by low dose of Streptozotocin, non-DM (healthy) mice are controls. Either vehicle or Metformin was administered twice daily via oral gavage for 7-days. Ferric chloride (FeCl3) arterial thrombosis and tail bleeding time were performed. Whole blood aggregometry, platelet activation/adhesion and mitochondrial bioenergetics were evaluated. RESULTS: Metformin decreased susceptibility of DM mice to arterial thrombosis. Platelet bioenergetics show DM mice have increased platelet mitochondrial respiration, but no differences were observed with Metformin treatment. In non-DM (healthy) mice, Metformin modulated ADP-dependent increase in platelet adhesion. Non-DM (healthy) mice, Metformin shortens bleeding time with faster thrombotic occlusion. Metformin also increased platelet mitochondrial maximal respiration and spare respiratory capacity uniquely in non-DM (healthy) mice. CONCLUSION: Metformin regulates platelet bioenergetics and ADP-mediated platelet function in DM mice which attenuates susceptibility to arterial thrombosis. Future studies will evaluate clinically relevant doses of Metformin that regulates thrombotic function in diabetic platelets. |
format | Online Article Text |
id | pubmed-10653203 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
record_format | MEDLINE/PubMed |
spelling | pubmed-106532032023-11-15 High Dose of Metformin Decreases Susceptibility to Occlusive Arterial Thrombosis in Diabetic Mice Alvidrez, Roberto I. Mota Annarapu, Gowtham K. Srinivasan, Amudan J. Liu, Zeyu Yazdani, Hamza O. Nolfi-Donegan, Deidre Simmons, Richard L. Shiva, Sruti Neal, Matthew D. J Pharm Pharmacol Res Article INTRODUCTION: Metformin is the most prescribed medication in Diabetes Mellitus(DM). Metformin has shown to decrease mean platelet volume, with promising antiplatelet effects. High doses of Metformin have also been associated with hypercoagulation. We hypothesize that Metformin will protect DM mice from occlusive arterial thrombus formation by altering platelet activation and mitochondrial bioenergetics. METHODS: DM was developed by low dose of Streptozotocin, non-DM (healthy) mice are controls. Either vehicle or Metformin was administered twice daily via oral gavage for 7-days. Ferric chloride (FeCl3) arterial thrombosis and tail bleeding time were performed. Whole blood aggregometry, platelet activation/adhesion and mitochondrial bioenergetics were evaluated. RESULTS: Metformin decreased susceptibility of DM mice to arterial thrombosis. Platelet bioenergetics show DM mice have increased platelet mitochondrial respiration, but no differences were observed with Metformin treatment. In non-DM (healthy) mice, Metformin modulated ADP-dependent increase in platelet adhesion. Non-DM (healthy) mice, Metformin shortens bleeding time with faster thrombotic occlusion. Metformin also increased platelet mitochondrial maximal respiration and spare respiratory capacity uniquely in non-DM (healthy) mice. CONCLUSION: Metformin regulates platelet bioenergetics and ADP-mediated platelet function in DM mice which attenuates susceptibility to arterial thrombosis. Future studies will evaluate clinically relevant doses of Metformin that regulates thrombotic function in diabetic platelets. 2023 2023-10-16 /pmc/articles/PMC10653203/ /pubmed/37975061 Text en https://creativecommons.org/licenses/by/4.0/This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license 4.0 |
spellingShingle | Article Alvidrez, Roberto I. Mota Annarapu, Gowtham K. Srinivasan, Amudan J. Liu, Zeyu Yazdani, Hamza O. Nolfi-Donegan, Deidre Simmons, Richard L. Shiva, Sruti Neal, Matthew D. High Dose of Metformin Decreases Susceptibility to Occlusive Arterial Thrombosis in Diabetic Mice |
title | High Dose of Metformin Decreases Susceptibility to Occlusive Arterial Thrombosis in Diabetic Mice |
title_full | High Dose of Metformin Decreases Susceptibility to Occlusive Arterial Thrombosis in Diabetic Mice |
title_fullStr | High Dose of Metformin Decreases Susceptibility to Occlusive Arterial Thrombosis in Diabetic Mice |
title_full_unstemmed | High Dose of Metformin Decreases Susceptibility to Occlusive Arterial Thrombosis in Diabetic Mice |
title_short | High Dose of Metformin Decreases Susceptibility to Occlusive Arterial Thrombosis in Diabetic Mice |
title_sort | high dose of metformin decreases susceptibility to occlusive arterial thrombosis in diabetic mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10653203/ https://www.ncbi.nlm.nih.gov/pubmed/37975061 |
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