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The basis for this mobilization defect is not completely understood, and we sought to determine if hyperglycemic conditions enhanced EPC adhesion. We found that culturing EPCs in high glucose media increased adhesion to bone marrow stromal cells. This enhanced adhesion was associated with decreased expression of protein kinase A regulatory subunit 1\u03b2 (PRKAR1\u03b2), activation of protein kinase A (PKA), and phosphorylation of \u03b14-integrin on serine 988. This potentiated adhesion was reversed by treatment with a PKA inhibitor, overexpression of PRKAR1\u03b2, or expression of a phosphorylation-defective \u03b14-integrin variant (\u03b14[S988A]). Using a model of type 1 diabetes, we showed that \u03b14(S988A)-expressing mice have more circulating EPCs than their wild-type counterparts. Moreover, diabetic \u03b14(S988A) mice demonstrate enhanced revascularization after hind limb ischemia. Thus, we have identified a novel signaling mechanism activating PKA in diabetes (downregulation of an inhibitory regulatory subunit) that leads to deficits of circulating EPCs and impaired vascular repair, which could be reversed by \u03b14-integrin mutation.<\/jats:p>","DOI":"10.2337\/db16-0634","type":"journal-article","created":{"date-parts":[[2016,8,6]],"date-time":"2016-08-06T02:28:38Z","timestamp":1470450518000},"page":"3505-3515","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":19,"title":["Enhanced Integrin \u03b14\u03b21\u2013Mediated Adhesion Contributes to a Mobilization Defect of Endothelial Progenitor Cells in Diabetes"],"prefix":"10.2337","volume":"65","author":[{"given":"Wesley T.","family":"Abplanalp","sequence":"first","affiliation":[{"name":"Diabetes and Obesity Center, University of Louisville, Louisville, KY"},{"name":"Department of Physiology, University of Louisville, Louisville, 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