title: Endothelin-1 inhibits adiponectin secretion through a phosphatidylinositol 4,5-bisphosphate/actin-dependent mechanism.
abstract: Adiponectin is an adipokine with profound insulin-sensitizing, anti-inflammatory, and anti-atherogenic properties. Plasma levels of adiponectin are reduced in insulin resistant states such as obesity, type 2 diabetes and cardiovascular disease. However, the mechanism(s) by which adiponectin concentrations are decreased during disease development is unclear. Studies have shown that endothelin-1 (ET-1), a vasoconstrictor peptide, affects adipocyte glucose metabolism and secretion of adipokines such as leptin, resistin, and adiponectin. The goal of our study was to determine the mechanism by which ET-1 decreases adiponectin secretion. 3T3-L1 adipocytes were treated for 24h with ET-1 (10nM) and then stimulated with vehicle or insulin (100 nM) for a period of 1-2h. Chronic ET-1 (24h) treatment significantly decreased basal and insulin-stimulated adiponectin secretion by 66% and 47%, respectively. Inhibition of phosphatidylinositol 4,5-bisphosphate (PIP(2)) hydrolysis by the PLCbeta inhibitor, U73122, or exogenous addition of PIP(2):histone carrier complex (1.25:0.625 microM) ameliorated the decrease in basal and insulin-stimulated adiponectin secretion observed with ET-1. However, treatment with exogenous PIP(2):histone carrier complex and the actin depolymerizing agent latrunculin B (20 microM) did not reverse the ET-1-mediated decrease in adiponectin secretion. In conclusion, we demonstrate that ET-1 inhibits basal and insulin-stimulated adiponectin secretion through PIP(2) modulation of the actin cytoskeleton.
authors: Boshell Diabetes and Metabolic Diseases Research Program, Department of Anatomy, Physiology and Pharmacology, Auburn University, USA.
authors: Deepa
authors: D
authors: Bedi
authors: Kristen J
authors: KJ
authors: Clarke
authors: John C
authors: JC
authors: Dennis
authors: Qiao
authors: Q
authors: Zhong
authors: Brandon L
authors: BL
authors: Brunson
authors: Edward E
authors: EE
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authors: Robert L
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