White Adipocyte Adiponectin Exocytosis Is Stimulated via {beta}3-Adrenergic Signaling and Activation of Epac1: Catecholamine Resistance in Obesity and Type 2 Diabetes

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 β3-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 β3AR 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 β3AR and Epac1 was reduced in adipocytes from obese animals, and corresponded to a respective ~35% and ~30% reduction at the protein level. Small interfering RNA–mediated knockdown of β3AR (~60%) and Epac1 (~50%) was associated with abrogated catecholamine-stimulated adiponectin secretion. We propose that adiponectin exocytosis is stimulated via adrenergic signaling pathways mainly involving β3ARs. We further suggest that adrenergically stimulated adiponectin secretion is disturbed in obesity/type 2 diabetes as a result of the reduced expression of β3ARs and Epac1 in a state we define as “catecholamine resistance.”

Diabetes Metabolism


White Adipocyte Adiponectin Exocytosis Is Stimulated via {beta}3-Adrenergic Signaling and Activation of Epac1: Catecholamine Resistance in Obesity and Type 2 Diabetes was first posted on November 9, 2016 at 10:16 pm.
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Reblogged 6 months ago from diabeticscareguide.com

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Amrita Wellness Medicine Clinic

Alina Porojan has been working as a natural medicine practitioner for the past twelve years, constantly educating herself and deepening her knowledge and clinical experience. Alina believes that health and healing is inherent to each of us, and sees her role as re-connecting us to our already existing potential for optimal health and wellness.