Knockout of endothelin-1 in vascular endothelial cells protects against insulin resistance induced by high-salt diet in mice.
The increased plasma Endothelin-1 (ET-1) level has been associated with development of insulin resistance in obese and hypertensive patients. However, the underlying mechanism remains elusive. Here we investigate the potential role of endothelial cell-derived ET-1 in mediating insulin resistance induced by high-salt diet. To address this issue, we used vascular endothelial cell-specific ET-1 knockout (VEETKO) mice and its littermates fed with a high-salt diet containing 8% NaCl for 3 weeks, and evaluated the metabolic parameters. High-salt diet increased systolic blood pressure similarly in both genotypes. We observed impairment of glucose tolerance in control mice despite comparable increase of serum insulin concentration with VEETKO mice. We further found that VEETKO mice showed preservation of circulating adiponectin level - an adipokine with insulin-sensitizing property - and prevention of the upregulation of the pro-inflammatory adipokine TNF-α, which lead towards better insulin sensitivity. These results provide evidence that blockade of endothelin signaling may be proven beneficial in preventing high-salt induced insulin resistance.
Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.
Naoko
N
Iwasa
Noriaki
N
Emoto
Bambang
B
Widyantoro
Kazuya
K
Miyagawa
Kazuhiko
K
Nakayama
Kenichi
K
Hirata
D052242:Adiponectin / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D019332:Endothelin-1 / Q000172:deficiency* / Q000235:genetics; D005951:Glucose Tolerance Test; D006339:Heart Rate; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D024821:Metabolic Syndrome / Q000209:etiology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D052242:Adiponectin; C499919:Adipoq protein, mouse; D019332:Endothelin-1; D017673:Sodium Chloride, Dietary; D014409:Tumor Necrosis Factor-alpha