| First Author | Komai AM | Year | 2016 |
| Journal | Diabetes | Volume | 65 |
| Issue | 11 | Pages | 3301-3313 |
| PubMed ID | 27554468 | Mgi Jnum | J:249471 |
| Mgi Id | MGI:5922276 | Doi | 10.2337/db15-1597 |
| Citation | Komai AM, et al. (2016) White Adipocyte Adiponectin Exocytosis Is Stimulated via beta3-Adrenergic Signaling and Activation of Epac1: Catecholamine Resistance in Obesity and Type 2 Diabetes. Diabetes 65(11):3301-3313 |
| abstractText | We investigated the physiological regulation of adiponectin exocytosis in health and metabolic disease by a combination of membrane capacitance patch-clamp recordings and biochemical measurements of short-term (30-min incubations) adiponectin secretion. Epinephrine or the beta3-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 beta3AR 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 beta3AR and Epac1 was reduced in adipocytes from obese animals, and corresponded to a respective approximately 35% and approximately 30% reduction at the protein level. Small interfering RNA-mediated knockdown of beta3AR ( approximately 60%) and Epac1 ( approximately 50%) was associated with abrogated catecholamine-stimulated adiponectin secretion. We propose that adiponectin exocytosis is stimulated via adrenergic signaling pathways mainly involving beta3ARs. We further suggest that adrenergically stimulated adiponectin secretion is disturbed in obesity/type 2 diabetes as a result of the reduced expression of beta3ARs and Epac1 in a state we define as "catecholamine resistance." |
