White Adipocyte Adiponectin Exocytosis Is Stimulated via ß3-Adrenergic Signaling and Activation of Epac1: Catecholamine Resistance in Obesity and Type 2 Diabetes.
Diabetes
; 65(11): 3301-3313, 2016 Nov.
Article
em En
| MEDLINE
| ID: mdl-27554468
ABSTRACT
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 ß3-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 ß3AR 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 ß3AR and Epac1 was reduced in adipocytes from obese animals, and corresponded to a respective â¼35% and â¼30% reduction at the protein level. Small interfering RNA-mediated knockdown of ß3AR (â¼60%) and Epac1 (â¼50%) was associated with abrogated catecholamine-stimulated adiponectin secretion. We propose that adiponectin exocytosis is stimulated via adrenergic signaling pathways mainly involving ß3ARs. We further suggest that adrenergically stimulated adiponectin secretion is disturbed in obesity/type 2 diabetes as a result of the reduced expression of ß3ARs and Epac1 in a state we define as "catecholamine resistance."
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Catecolaminas
/
Diabetes Mellitus Tipo 2
/
Adipócitos Brancos
Limite:
Animals
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2016
Tipo de documento:
Article