Regulation of adiponectin secretion by endothelin-1.
Adiponectin is an adipocyte-derived hormone best known for its insulin-sensitizing ability. The expression and circulating concentration of adiponectin are decreased in type 2 diabetics and increase following treatment with thiazolidinediones. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide whose levels are elevated in numerous disease states, including obesity and diabetes. ET-1 has profound effects on adipose tissue metabolism and alters the release of adipose-derived factors such as leptin and resistin, therefore we investigated the role of ET-1 in adiponectin secretion. 3T3-L1 adipocytes were treated with insulin (100 nM), ET-1 (100 nM), or the appropriate vehicle and adiponectin secretion into the media was determined by immunoblotting and densitometric analysis. Adiponectin secretion significantly increased 1h following insulin or ET-1 treatment, respectively. Pretreatment with ET-1 for 24h significantly inhibited the ability of insulin or ET-1 to acutely stimulate adiponectin secretion. The specific ET(A) receptor antagonist, BQ-610 (1 microM), significantly inhibited ET-1-stimulated adiponectin secretion. In summary, ET-1 acutely stimulates adiponectin secretion through the ET(A) receptor. Chronic exposure to ET-1 dramatically decreases the stimulatory effect of insulin and ET-1 on adiponectin secretion. Our findings suggest vascular factors such as ET-1 may play a role in the regulation of adiponectin secretion and whole body energy metabolism.
Clarke
Kristen J
KJ
Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849-5518, USA.
Zhong
Qiao
Q
Schwartz
Dean D
DD
Coleman
Elaine S
ES
Kemppainen
Robert J
RJ
Judd
Robert L
RL
D041721:3T3-L1 Cells / Q000166:cytology / Q000378:metabolism*; D000222:Adaptation, Physiological / Q000502:physiology; D052242:Adiponectin; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D019332:Endothelin-1 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D052242:Adiponectin; D019332:Endothelin-1; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins