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Epinephrine or the \u03b23-adrenergic receptor (AR) agonist CL 316,243 (CL) stimulated adiponectin exocytosis\/secretion in cultured 3T3-L1 and in primary subcutaneous mouse adipocytes, and the stimulation was inhibited by the Epac (Exchange Protein directly Activated by cAMP) antagonist ESI-09. The \u03b23AR was highly expressed in cultured and primary adipocytes, whereas other ARs were detected at lower levels. 3T3-L1 and primary adipocytes expressed Epac1, whereas Epac2 was undetectable. Adiponectin secretion could not be stimulated by epinephrine or CL in adipocytes isolated from obese\/type 2 diabetic mice, whereas the basal (unstimulated) adiponectin release level was elevated twofold. Gene expression of \u03b23AR and Epac1 was reduced in adipocytes from obese animals, and corresponded to a respective \u223c35% and \u223c30% reduction at the protein level. Small interfering RNA\u2013mediated knockdown of \u03b23AR (\u223c60%) and Epac1 (\u223c50%) was associated with abrogated catecholamine-stimulated adiponectin secretion. We propose that adiponectin exocytosis is stimulated via adrenergic signaling pathways mainly involving \u03b23ARs. We further suggest that adrenergically stimulated adiponectin secretion is disturbed in obesity\/type 2 diabetes as a result of the reduced expression of \u03b23ARs and Epac1 in a state we define as \u201ccatecholamine resistance.\u201d<\/jats:p>","DOI":"10.2337\/db15-1597","type":"journal-article","created":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T02:59:42Z","timestamp":1472007582000},"page":"3301-3313","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":51,"title":["White Adipocyte Adiponectin Exocytosis Is Stimulated via \u03b23-Adrenergic Signaling and Activation of Epac1: Catecholamine Resistance in Obesity and Type 2 Diabetes"],"prefix":"10.2337","volume":"65","author":[{"given":"Ali M.","family":"Komai","sequence":"first","affiliation":[{"name":"Department of Physiology\/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, G\u00f6teborg, 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