White Adipocyte Adiponectin Exocytosis Is Stimulated via β3-Adrenergic Signaling and Activation of Epac1: Catecholamine Resistance in Obesity and Type 2 Diabetes
| Autor: | Charlotta S. Olofsson, Marcus Johansson, Ingrid Wernstedt Asterholm, Mickaël F. El Hachmane, Ali M. Komai, Ahmed Alrifaiy, Eduard Peris, Saliha Musovic |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism Adipocytes White Adrenergic Dioxoles Biology Exocytosis 03 medical and health sciences Mice 0302 clinical medicine Catecholamines Internal medicine 3T3-L1 Cells Internal Medicine medicine Adipocytes Animals Guanine Nucleotide Exchange Factors Secretion Adiponectin secretion Obesity Receptor Cells Cultured Adiponectin Hydrazones Isoxazoles Electrophysiology Mice Inbred C57BL 030104 developmental biology Endocrinology Diabetes Mellitus Type 2 Receptors Adrenergic beta-3 Catecholamine Signal transduction 030217 neurology & neurosurgery medicine.drug Signal Transduction |
| Zdroj: | Diabetes. 65(11) |
| ISSN: | 1939-327X |
| Popis: | 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.” |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|