{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:04:17Z","timestamp":1790913857983,"version":"4.1.0"},"reference-count":45,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:p>Although mutations in the \u03b3-subunit of AMP-activated protein kinase (AMPK) can result in excessive glycogen accumulation and cardiac hypertrophy, the mechanisms by which this occurs have not been well defined. Because &gt;65% of cardiac AMPK activity is associated with the \u03b31-subunit of AMPK, we investigated the effects of expression of an AMPK-activating \u03b31-subunit mutant (\u03b31 R70Q) on regulatory pathways controlling glycogen accumulation and cardiac hypertrophy in neonatal rat cardiac myocytes. Whereas expression of \u03b31 R70Q displayed the expected increase in palmitate oxidation rates, rates of glycolysis were significantly depressed. In addition, glycogen synthase activity was increased in cardiac myocytes expressing \u03b31 R70Q, due to both increased expression and decreased phosphorylation of glycogen synthase. The inhibition of glycolysis and increased glycogen synthase activity were correlated with elevated glycogen levels in \u03b31 R70Q-expressing myocytes. In association with the reduced phosphorylation of glycogen synthase, glycogen synthase kinase (GSK)-3\u03b2 protein and mRNA levels were profoundly decreased in the \u03b31 R70Q-expressing myocytes. Consistent with GSK-3\u03b2 negatively regulating hypertrophy via inhibition of nuclear factor of activated T cells (NFAT), the dramatic downregulation of GSK-3\u03b2 was associated with increased nuclear activity of NFAT. Together, these data provide important new information about the mechanisms by which a mutation in the \u03b3-subunit of AMPK causes altered AMPK signaling and identify multiple pathways involved in regulating both cardiac myocyte metabolism and growth that may contribute to the development of the \u03b3 mutant-associated cardiomyopathy.<\/jats:p>","DOI":"10.1152\/ajpheart.00936.2007","type":"journal-article","created":{"date-parts":[[2007,9,29]],"date-time":"2007-09-29T01:18:27Z","timestamp":1191028707000},"page":"H3456-H3464","source":"Crossref","is-referenced-by-count":7,"title":["The AMPK \u03b31 R70Q mutant regulates multiple metabolic and growth pathways in neonatal cardiac myocytes"],"prefix":"10.1152","volume":"293","author":[{"given":"Karalyn D.","family":"Folmes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee A.","family":"Witters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Allard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin E.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R. 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