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Carvedilol is superior in effectiveness to other drugs that are used for similar indications and does not cause insulin resistance or diabetes, which can occur with other \u03b2\u2010antagonists. We have shown that carvedilol increased glucose usage in C2C12 cells. We investigate the biased agonist efficacy of carvedilol on \u03b2\u2010arrestins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Streptozotocin (STZ)\u2010induced diabetes rat model was used to induce metabolic and cardiac disorders. After 8 weeks of diabetes, animals were treated with carvedilol or vehicle for another 4 weeks. In vitro heart function was evaluated at baseline as well as with increasing concentrations of isoprenaline. Effects of diabetes and carvedilol treatment on \u03b2\u2010arrestins, ERK, PPAR\u03b1, CD36 proteins and pyruvate kinase activity were evaluated. \u03b2\u2010arrestins were silenced in C2C12 cells by using siRNA. Acute effects of carvedilol on ERK, CD36, mitochondrial transcription factor A, cardiolipin proteins and citrate synthase activity were investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Carvedilol reversed the deterioration of cardiac function in diabetes and diabetes\u2010induced decrease in \u03b2\u2010arrestins in rats. Carvedilol decreased the expression of CD36 in diabetes and increased mitochondrial transcription factor A and cardiolipin proteins. Silencing of \u03b2\u2010arrestins in cells prevented the effects of carvedilol on these proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>The metabolic effects of carvedilol seem to be related to biased activation of \u03b2\u2010arrestins. Patients with cardiovascular and metabolic disorders may benefit from new compounds that selectively act on \u03b2\u2010arrestins.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15269","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T18:44:41Z","timestamp":1601318681000},"page":"5580-5594","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Metabolic effects of carvedilol through \u03b2\u2010arrestin proteins: investigations in a streptozotocin\u2010induced diabetes rat model and in C2C12 myoblasts"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9181-3741","authenticated-orcid":false,"given":"Berna","family":"G\u00fcven","sequence":"first","affiliation":[{"name":"Department of Pharmacology Ankara University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2155-0100","authenticated-orcid":false,"given":"Z\u00fcmra","family":"Kara","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Ankara University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6883-1757","authenticated-orcid":false,"given":"Arzu","family":"Onay\u2010Be\u015fikci","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Ankara University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"issue":"1","key":"e_1_2_12_3_1","first-page":"S21","article-title":"The concise guide to pharmacology 2019\/20: G protein\u2010coupled receptors","volume":"176","author":"Alexander S. 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