{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:33:44Z","timestamp":1790883224432,"version":"4.1.0"},"reference-count":12,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T00:00:00Z","timestamp":1555891200000},"content-version":"vor","delay-in-days":67,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["TL1-TR-001875"],"award-info":[{"award-number":["TL1-TR-001875"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-AG-048022"],"award-info":[{"award-number":["R01-AG-048022"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-HL-126547-01"],"award-info":[{"award-number":["R01-HL-126547-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54-HL-112311"],"award-info":[{"award-number":["U54-HL-112311"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:p>Patients with type 1 diabetes mellitus (T1DM) have increased thrombosis and platelet activation. The mechanisms for platelet hyperactivation in diabetes are incompletely understood. T1DM is accompanied by hyperglycemia, dyslipidemia, and increased inflammation in addition to an altered hormonal milieu. In vitro analysis of platelets revealed that normal glucose reduces platelet activation whereas hyperglycemic conditions increase platelet activation. We therefore hypothesized that hyperglycemia increases platelet glucose utilization, which increases platelet activation to promote thrombosis. Glucose uptake and glycolysis were increased in platelets isolated from mice given streptozotocin (STZ) to induce T1DM in concert with induction of GLUT3. Platelets from STZ-induced diabetic mice exhibited increased activation after administration of protease-activated receptor 4 peptide and convulxin. In contrast, platelets isolated from GLUT1 and GLUT3 double-knockout (DKO) mice, which lack the ability to use glucose, failed to increase activation in hyperglycemic mice. Diabetic mice displayed decreased survival in a collagen\/epinephrine-induced pulmonary embolism model of in vivo platelet activation relative to nondiabetic controls. Survival after pulmonary embolism was increased in diabetic DKO mice relative to nondiabetic controls. These data reveal that increased platelet glucose metabolism in vivo contributes to increased platelet activation and thrombosis in a model of T1DM.<\/jats:p>","DOI":"10.2337\/db18-0981","type":"journal-article","created":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T01:15:45Z","timestamp":1550193345000},"page":"932-938","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":55,"title":["Glucose Metabolism Is Required for Platelet Hyperactivation in a Murine Model of Type 1 Diabetes"],"prefix":"10.2337","volume":"68","author":[{"given":"Trevor P.","family":"Fidler","sequence":"first","affiliation":[{"name":"Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, IA"},{"name":"Division of Molecular Medicine, Department of Medicine, Columbia University Medical Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Marti","sequence":"additional","affiliation":[{"name":"Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn","family":"Gerth","sequence":"additional","affiliation":[{"name":"Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Middleton","sequence":"additional","affiliation":[{"name":"Molecular Medicine Program, Department of Internal Medicine, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Molecular Medicine Program, Department of Internal Medicine, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T.","family":"Rondina","sequence":"additional","affiliation":[{"name":"Molecular Medicine Program, Department of Internal Medicine, University of Utah, Salt Lake City, UT"},{"name":"Geriatric Research, Education, and Clinical Center, Department of Internal Medicine, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.","family":"Weyrich","sequence":"additional","affiliation":[{"name":"Molecular Medicine Program, Department of Internal Medicine, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5290-0738","authenticated-orcid":false,"given":"E. Dale","family":"Abel","sequence":"additional","affiliation":[{"name":"Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, IA"},{"name":"Molecular Medicine Program, Department of Internal Medicine, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2019,2,14]]},"reference":[{"key":"2022031303371574500_B1","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1161\/01.CIR.99.2.224","article-title":"In vivo formation of 8-iso-prostaglandin f2alpha and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation","volume":"99","author":"Dav\u00ec","year":"1999","journal-title":"Circulation"},{"key":"2022031303371574500_B2","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1111\/jth.12170","article-title":"Enhanced platelet activity 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