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Store\u2010operated Ca<jats:sup>2+<\/jats:sup> channels (SOCCs) have been implicated in many diabetic complications. Vascular dysfunction is common in patients with diabetes, but the role of SOCCs in diabetic vasculopathy is still unclear. Our research aimed to investigate the effects of high glucose (HG) on store\u2010operated Ca<jats:sup>2+<\/jats:sup> entry (SOCE) in small arteries. Small mesenteric arteries from type 2 diabetic Zucker fatty rats (ZDF) versus their non\u2010diabetic controls (Zucker lean, ZL) were examined in a pressurized myograph. Vascular smooth muscle cells (VSMC) were isolated and intracellular Ca<jats:sup>2+<\/jats:sup> was measured (Fura 2\u2010AM). A specific protocol to deplete intracellular Ca<jats:sup>2+<\/jats:sup> stores and thereby open SOCCs, as well as pharmacological SOCE inhibitors (SKF\u201096365, BTP\u20102), were used to artificially activate and inhibit SOCE, respectively. High glucose (40\u00a0mmol\/L) relaxed arteries in a SKF\u2010sensitive manner. Diabetic arteries exhibited reduced HG\u2010induced relaxation, as well as reduced contraction after Ca<jats:sup>2+<\/jats:sup> replenishment. Further, the rise in intracellular Ca<jats:sup>2+<\/jats:sup> on account of SOCE is diminished in diabetic versus non\u2010diabetic VSMCs and was insensitive to HG in diabetic VSMCs. The expression of SOCC proteins was measured, detecting a downregulation of Orai1 in diabetes. In conclusion, diabetes leads to a reduction of SOCE and SOCE\u2010induced contraction, which is unresponsive to HG\u2010mediated inhibition. The reduced expression of Orai1 in diabetic arteries could account for the observed reduction in SOCE.<\/jats:p>","DOI":"10.1111\/1440-1681.13300","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T08:50:05Z","timestamp":1583743805000},"page":"1145-1157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Reduced store\u2010operated Ca<sup>2+<\/sup> entry impairs mesenteric artery function in response to high external glucose in type 2 diabetic ZDF rats"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9560-4015","authenticated-orcid":false,"given":"Christian","family":"Schach","sequence":"first","affiliation":[{"name":"Abteilung f\u00fcr Kardiologie Klinik und Poliklinik f\u00fcr Innere Medizin II Universit\u00e4res Herzzentrum Regensburg Universit\u00e4tsklinikum Regensburg Regensburg 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